bims-mibica Biomed News
on Mitochondrial bioenergetics in cancer
Issue of 2024‒08‒04
fifteen papers selected by
Kelsey Fisher-Wellman, Wake Forest University
  1. The ATP-driven extractor ATAD1/Msp1 proof-reads protein translocation into mitochondria.
  2. Carcinoma-associated mesenchymal stem cells promote ovarian cancer heterogeneity and metastasis through mitochondrial transfer.
  3. LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation.
  4. ASCT2 is a major contributor to serine uptake in cancer cells.
  5. Etomoxir-carnitine, a novel pharmaco-metabolite of etomoxir, inhibits phospholipases A2 and mitochondrial respiration.
  6. SLC45A4 encodes a mitochondrial putrescine transporter that promotes GABA de novo synthesis.
  7. Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA.
  8. DAP3 promotes mitochondrial activity and tumour progression in hepatocellular carcinoma by regulating MT-ND5 expression.
  9. Tumor-derived mitochondrial formyl peptides suppress tumor immunity through modification of the tumor microenvironment.
  10. The Warburg Effect Revisited through Blood and Electron Flow.
  11. MGA deletion leads to Richter's transformation by modulating mitochondrial OXPHOS.
  12. Mitochondrial Targetable Turn-On Fluorescent Probe for Fast Detection of NAD(P)H in Living Cells and In Vivo.
  13. Searching for Proton Transfer Channels in Respiratory Complex I.
  14. FAS Inhibited Proteomics and Phosphoproteomics Profiling of Colorectal Cancer Spheroids Shows Activation of Ferroptotic Death Mechanism.
  15. AutoMitoNetwork: Software for analyzing mitochondrial networks in autofluorescence images to enable label-free cell classification.
  1. Trends Cell Biol. 2024 Jul 31. pii: S0962-8924(24)00145-4. [Epub ahead of print]
    The ATP-driven extractor ATAD1/Msp1 proof-reads protein translocation into mitochondria.
    Maria Bohnert, Christos Gatsogiannis, Johannes M Herrmann.
      The accumulation of translocation intermediates in the mitochondrial import machinery threatens cellular fitness and is associated with cancer and neurodegeneration. A recent study by Weidberg and colleagues identifies ATAD1 as an ATP-driven extraction machine on the mitochondrial surface that pulls precursors into the cytosol to prevent clogging of mitochondrial import pores.
    Keywords:  AAA protein; cancer; integrated stress response (ISR); mitochondria; protein import; quality control
    DOI:  https://doi.org/10.1016/j.tcb.2024.07.007
  2. Cell Rep. 2024 Jul 26. pii: S2211-1247(24)00880-5. [Epub ahead of print]43(8): 114551
    Carcinoma-associated mesenchymal stem cells promote ovarian cancer heterogeneity and metastasis through mitochondrial transfer.
    Leonard Frisbie, Catherine Pressimone, Emma Dyer, Roja Baruwal, Geyon Garcia, Claudette St Croix, Simon Watkins, Michael Calderone, Grace Gorecki, Zaineb Javed, Huda I Atiya, Nadine Hempel, Alexander Pearson, Lan G Coffman.
      Ovarian cancer is characterized by early metastatic spread. This study demonstrates that carcinoma-associated mesenchymal stromal cells (CA-MSCs) enhance metastasis by increasing tumor cell heterogeneity through mitochondrial donation. CA-MSC mitochondrial donation preferentially occurs in ovarian cancer cells with low levels of mitochondria ("mito poor"). CA-MSC mitochondrial donation rescues the phenotype of mito poor cells, restoring their proliferative capacity, resistance to chemotherapy, and cellular respiration. Receipt of CA-MSC-derived mitochondria induces tumor cell transcriptional changes leading to the secretion of ANGPTL3, which enhances the proliferation of tumor cells without CA-MSC mitochondria, thus amplifying the impact of mitochondrial transfer. Donated CA-MSC mitochondrial DNA persisted in recipient tumor cells for at least 14 days. CA-MSC mitochondrial donation occurs in vivo, enhancing tumor cell heterogeneity and decreasing mouse survival. Collectively, this work identifies CA-MSC mitochondrial transfer as a critical mediator of ovarian cancer cell survival, heterogeneity, and metastasis and presents a unique therapeutic target in ovarian cancer.
    Keywords:  CP: Cancer; carcinoma-associated mesenchymal stem cells; metastasis; mitochondrial donation; ovarian cancer; oxidative phosphorylation; tumor heterogenity; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.celrep.2024.114551
  3. Nucleic Acids Res. 2024 Aug 01. pii: gkae662. [Epub ahead of print]
    LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation.
    Diana Rubalcava-Gracia, Kristina Bubb, Fredrik Levander, Stephen P Burr, Amelie V August, Patrick F Chinnery, Camilla Koolmeister, Nils-Göran Larsson.
      In mammals, the leucine-rich pentatricopeptide repeat protein (LRPPRC) and the stem-loop interacting RNA-binding protein (SLIRP) form a complex in the mitochondrial matrix that is required throughout the life cycle of most mitochondrial mRNAs. Although pathogenic mutations in the LRPPRC and SLIRP genes cause devastating human mitochondrial diseases, the in vivo function of the corresponding proteins is incompletely understood. We show here that loss of SLIRP in mice causes a decrease of complex I levels whereas other OXPHOS complexes are unaffected. We generated knock-in mice to study the in vivo interdependency of SLIRP and LRPPRC by mutating specific amino acids necessary for protein complex formation. When protein complex formation is disrupted, LRPPRC is partially degraded and SLIRP disappears. Livers from Lrpprc knock-in mice had impaired mitochondrial translation except for a marked increase in the synthesis of ATP8. Furthermore, the introduction of a heteroplasmic pathogenic mtDNA mutation (m.C5024T of the tRNAAla gene) into Slirp knockout mice causes an additive effect on mitochondrial translation leading to embryonic lethality and reduced growth of mouse embryonic fibroblasts. To summarize, we report that the LRPPRC/SLIRP protein complex is critical for maintaining normal complex I levels and that it also coordinates mitochondrial translation in a tissue-specific manner.
    DOI:  https://doi.org/10.1093/nar/gkae662
  4. Cell Rep. 2024 Jul 26. pii: S2211-1247(24)00881-7. [Epub ahead of print]43(8): 114552
    ASCT2 is a major contributor to serine uptake in cancer cells.
    Kelly O Conger, Christopher Chidley, Mete Emir Ozgurses, Huiping Zhao, Yumi Kim, Svetlana E Semina, Philippa Burns, Vipin Rawat, Lina Lietuvninkas, Ryan Sheldon, Issam Ben-Sahra, Jonna Frasor, Peter K Sorger, Gina M DeNicola, Jonathan L Coloff.
      The non-essential amino acid serine is a critical nutrient for cancer cells due to its diverse biosynthetic functions. While some tumors can synthesize serine de novo, others are auxotrophic and therefore reliant on serine uptake. Importantly, despite several transporters being known to be capable of transporting serine, the transporters that mediate serine uptake in cancer cells are not known. Here, we characterize the amino acid transporter ASCT2 (SLC1A5) as a major contributor to serine uptake in cancer cells. ASCT2 is well known as a glutamine transporter in cancer, and our work demonstrates that serine and glutamine compete for uptake through ASCT2. We further show that ASCT2-mediated serine uptake is essential for purine nucleotide biosynthesis and that estrogen receptor α (ERα) promotes serine uptake by directly activating SLC1A5 transcription. Collectively, our work defines an additional important role for ASCT2 as a serine transporter in cancer and evaluates ASCT2 as a potential therapeutic target.
    Keywords:  ASCT2; CP: Cancer; ERα; SLC1A5; amino acid uptake; breast cancer; cancer metabolism; diet; purine biosynthesis; serine starvation; serine transporter
    DOI:  https://doi.org/10.1016/j.celrep.2024.114552
  5. J Lipid Res. 2024 Jul 31. pii: S0022-2275(24)00116-0. [Epub ahead of print] 100611
    Etomoxir-carnitine, a novel pharmaco-metabolite of etomoxir, inhibits phospholipases A2 and mitochondrial respiration.
    Sung Ho Moon, Xinping Liu, Christopher M Jenkins, Beverly Gibson Dilthey, Gary J Patti, Richard W Gross.
      Mitochondrial fatty acid oxidation serves as an essential process for cellular survival, differentiation, proliferation, and energy metabolism. Numerous studies have utilized etomoxir (ETO) for the irreversible inhibition of carnitine palmitoylcarnitine transferase 1 (CPT1) which catalyzes the rate-limiting step for mitochondrial long-chain fatty acid β-oxidation to examine the bioenergetic roles of mitochondrial fatty acid metabolism in many tissues in multiple diverse disease states. Herein, we demonstrate that intact mitochondria robustly metabolize etomoxir to etomoxir-carnitine (ETO-carnitine) prior to nearly complete etomoxir-mediated inhibition of CPT1. The novel pharmaco-metabolite, ETO-carnitine, was conclusively identified by accurate mass, fragmentation patterns, and isotopic fine structure. On the basis of these data, ETO-carnitine was successfully differentiated from isobaric structures (e.g., 3-hydroxy-C18:0 carnitine and 3-hydroxy-C18:1 carnitine). Mechanistically, generation of ETO-carnitine from mitochondria required exogenous Mg2+, ATP or ADP, CoASH, and L-carnitine indicating that thioesterification by long-chain acyl-CoA synthetase to form ETO-CoA precedes its conversion to ETO-carnitine by CPT1. CPT1-dependent generation of ETO-carnitine was substantiated by an orthogonal approach using ST1326 (a CPT1 inhibitor) which effectively inhibits mitochondrial ETO-carnitine production. Surprisingly, purified ETO-carnitine potently inhibited calcium-independent PLA2γ and PLA2β as well as mitochondrial respiration independent of CPT1. Robust production and release of ETO-carnitine from HepG2 cells incubated in the presence of ETO was also demonstrated. Collectively, this study identifies the chemical mechanism for the biosynthesis of a novel pharmaco-metabolite of etomoxir, ETO-carnitine, that is generated by CPT1 in mitochondria and likely impacts multiple downstream (non-CPT1 related) enzymes and processes in multiple subcellular compartments.
    Keywords:  Lipidomics; Lipids/Chemistry; Lipolysis and fatty acid metabolism; carnitine palmitoyltransferase (CPT); etomoxir; etomoxir-carnitine; mitochondria; off-target effects; pharmaco-metabolite; phospholipases A(2)
    DOI:  https://doi.org/10.1016/j.jlr.2024.100611
  6. bioRxiv. 2024 Jul 24. pii: 2024.07.23.604788. [Epub ahead of print]
    SLC45A4 encodes a mitochondrial putrescine transporter that promotes GABA de novo synthesis.
    Cecilia Colson, Yujue Wang, James Atherton, Xiaoyang Su.
      Solute carriers (SLC) are membrane proteins that facilitate the transportation of ions and metabolites across either the plasma membrane or the membrane of intracellular organelles. With more than 450 human genes annotated as SLCs, many of them are still orphan transporters without known biochemical functions. We developed a metabolomic-transcriptomic association analysis, and we found that the expression of SLC45A4 has a strong positive correlation with the cellular level of γ-aminobutyric acid (GABA). Using mass spectrometry and the stable isotope tracing approach, we demonstrated that SLC45A4 promotes GABA de novo synthesis through the Arginine/Ornithine/Putrescine (AOP) pathway. SLC45A4 functions as a putrescine transporter localized to the mitochondrial membrane to facilitate GABA production. Taken together, our results revealed a new biochemical mechanism where SLC45A4 controls GABA production.
    DOI:  https://doi.org/10.1101/2024.07.23.604788
  7. bioRxiv. 2024 Jul 19. pii: 2024.07.18.604121. [Epub ahead of print]
    Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA.
    Brett T Wisniewski, Laura L Lackner.
      Mitochondria exist as dynamic tubular networks and the morphology of these networks impacts organelle function and cell health. Mitochondrial morphology is maintained in part by the opposing activities of mitochondrial fission and fusion. Mitochondrial fission and fusion are also required to maintain mitochondrial DNA (mtDNA) integrity. In Saccharomyces cerevisiae , the simultaneous inhibition of mitochondrial fission and fusion results in increased mtDNA mutation and the consequent loss of respiratory competence. The mechanism by which fission and fusion maintain mtDNA integrity is not fully understood. Previous work demonstrates that mtDNA is spatially linked to mitochondrial fission sites. Here, we extend this finding using live-cell imaging to localize mtDNA to mitochondrial fusion sites. While mtDNA is present at sites of mitochondrial fission and fusion, mitochondrial fission and fusion rates are not altered in cells lacking mtDNA. Using alleles that alter mitochondrial fission and fusion rates, we find that mtDNA integrity can be maintained in cells with significantly reduced, but balanced, rates of fission and fusion. In addition, we find that increasing mtDNA copy number reduces the loss of respiratory competence in double mitochondrial fission-fusion mutants. Our findings add novel insights into the relationship between mitochondrial dynamics and mtDNA integrity.
    DOI:  https://doi.org/10.1101/2024.07.18.604121
  8. Cell Death Dis. 2024 Jul 29. 15(7): 540
    DAP3 promotes mitochondrial activity and tumour progression in hepatocellular carcinoma by regulating MT-ND5 expression.
    Siyu Tan, Xiao Zhang, Xiaowei Guo, Guoqiang Pan, Lunjie Yan, Ziniu Ding, Ruizhe Li, Dongxu Wang, Yuchuan Yan, Zhaoru Dong, Tao Li.
      Cancer cells often exhibit fragmented mitochondria and dysregulated mitochondrial dynamics, but the underlying mechanism remains elusive. Here, we found that the mitochondrial protein death-associated protein 3 (DAP3) is localized to mitochondria and promotes the progression of hepatocellular carcinoma (HCC) by regulating mitochondrial function. DAP3 can promote the proliferation, migration, and invasion of HCC cells in vitro and in vivo by increasing mitochondrial respiration, inducing the epithelial-mesenchymal transition (EMT), and slowing cellular senescence. Mechanistically, DAP3 can increase mitochondrial complex I activity in HCC cells by regulating the translation and expression of MT-ND5. The phosphorylation of DAP3 at Ser185 mediated by AKT is the key event mediating the mitochondrial localization and function of DAP3 in HCC cells. In addition, the DAP3 expression in HCC samples is inversely correlated with patient survival. Our results revealed a mechanism by which DAP3 promotes mitochondrial function and HCC progression by regulating MT-ND5 translation and expression, indicating that DAP3 may be a therapeutic target for HCC.
    DOI:  https://doi.org/10.1038/s41419-024-06912-2
  9. Cancer Sci. 2024 Jul 31.
    Tumor-derived mitochondrial formyl peptides suppress tumor immunity through modification of the tumor microenvironment.
    Kayoko Waki, Miyako Ozawa, Keisuke Ohta, Nobukazu Komatsu, Akira Yamada.
      Mitochondrial N-formylpeptides are released from damaged or dead cells to the extracellular spaces and cause inflammatory responses. The role of mitochondrial N-formylpeptides in aseptic systemic inflammatory response syndromes induced by trauma or cardiac surgery has been well investigated. However, there are no reports regarding the role of mitochondrial N-formylpeptides in cancer. In this study, we investigated the role of tumor cell-derived mitochondrial N-formylpeptides in anti-tumor immunity using knockout murine tumor cells of mitochondrial methionyl-tRNA formyltransferase (MTFMT), which catalyze N-formylation of mitochondrial DNA-encoded proteins. There was no apparent difference among the wild-type and MTFMT-knockout clones of E.G7-OVA cells with respect to morphology, mitochondrial dynamics, glycolysis and oxidative phosphorylation, oxygen consumption rate, or in vitro cell growth. In contrast, in vivo tumor growth of MTFMT-knockout cells was slower than that of wild-type cells. A reduced number of myeloid-derived suppressor cells and an increase of cytotoxic T-lymphocytes in the tumor tissues were observed in the MTFMT-knockout tumors. These results suggested that tumor cell-derived mitochondrial N-formylpeptides had a negative role in the host anti-tumor immunity through modification of the tumor microenvironment.
    Keywords:  DAMPs; alarmin; mitochondrial formyl peptide; tumor immunity; tumor microenvironment
    DOI:  https://doi.org/10.1111/cas.16266
  10. Cancer Res. 2024 Jul 02. 84(13): 2046-2048
    The Warburg Effect Revisited through Blood and Electron Flow.
    Yahui Wang, Chi V Dang.
      The Warburg effect describes the propensity of many cancers to consume glucose avidly and convert it to lactate in the presence of oxygen. The benefit of the Warburg effect on cancer cells remains enigmatic, particularly because extracellular disposal of incompletely oxidized lactate is wasteful. However, lactate is not discarded from the body, but rather recycled as pyruvate for metabolism through the tricarboxylic acid cycle in oxidative tissues and cells. Hence, tissue and interorgan metabolism play important roles in tumor metabolism. The production of tumor lactate to be recycled elsewhere parallels the Cori cycle, in which lactate produced by muscle activity is shuttled to the liver, where it is converted to pyruvate and subsequently stored as glucose moieties in glycogen. This perspective will consider this organismal contextwhile discussing how glucose is used in tumors. We highlight several key articles published decades ago in Cancer Research that are foundational to our current understanding of cancer biology and metabolism.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-24-0474
  11. Sci Transl Med. 2024 Jul 31. 16(758): eadg7915
    MGA deletion leads to Richter's transformation by modulating mitochondrial OXPHOS.
    Prajish Iyer, Bo Zhang, Tingting Liu, Meiling Jin, Kevyn Hart, Jibin Zhang, Viola Siegert, Marianne Remke, Xuesong Wang, Lei Yu, Joo Song, Girish Venkataraman, Wing C Chan, Zhenyu Jia, Maike Buchner, Tanya Siddiqi, Steven T Rosen, Alexey Danilov, Lili Wang.
      Richter's transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. MGA (Max gene associated), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms of MGA deletion that drive CLL to RT remain elusive. We established an RT mouse model by knockout of Mga in the Sf3b1/Mdr CLL model using CRISPR-Cas9 to determine the role of Mga in RT. Murine RT cells exhibited mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). Through RNA sequencing and functional characterization, we identified Nme1 (nucleoside diphosphate kinase) as an Mga target, which drives RT by modulating OXPHOS. Given that NME1 is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and electron transport chain complex II substantially prolongs the survival of RT mice in vivo. Our results suggest that the Mga-Nme1 axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a potential therapeutic avenue for RT.
    DOI:  https://doi.org/10.1126/scitranslmed.adg7915
  12. ACS Appl Bio Mater. 2024 Jul 29.
    Mitochondrial Targetable Turn-On Fluorescent Probe for Fast Detection of NAD(P)H in Living Cells and In Vivo.
    Kuppan Magesh, Lu Yueh Hsun, Shu Pao Wu, Sivan Velmathi.
      Using colorimetric and fluorescent probes has garnered significant interest in detecting NAD(P)H within practical systems and biological organisms. Herein, we synthesized a mitochondrial targetable fluorescent probe (ISQM) for fast NAD(P)H detection in <1 min. The ISQM is positively impacted because of the quinolinium reduction facilitated by NAD(P)H. It consequently liberates the push-pull fluorophore ISQM-H with a large Stokes shift (110 nm). This release leads to a turn-on response of red-emitting fluorescence, accompanied by a meager detection limit of 59 nM. To compare the differences in the NAD(P)H levels of tumor cells and normal cells, we used ISQM to measure the fluorescent signal intensities of HeLa cells (tumor cells) and RAW 264.7 cells (normal cells), respectively. Surprisingly, the experiment, including the measurement of colocalization over time, indicated that the probe exhibits a reaction with mitochondrial NAD(P)H and trace NAD(P)H in hypoxia conditions in cancer cells. Moreover, we effectively used the probe ISQM to identify the NAD(P)H in tumor mice.
    Keywords:  NAD(P)H; cell imaging; mice; mitochondria; tumor
    DOI:  https://doi.org/10.1021/acsabm.4c00755
  13. Biophys J. 2024 Aug 01. pii: S0006-3495(24)00518-6. [Epub ahead of print]
    Searching for Proton Transfer Channels in Respiratory Complex I.
    Panyue Wang, Jackson Demaray, Stanislav Moroz, Alexei A Stuchebrukhov.
      We have explored a strategy to identify potential proton transfer channels using computational analysis of a protein structure based on Voronoi partitioning, and applied it for the analysis of proton transfer pathways in redox-driven proton pumping respiratory complex I. The analysis results in a network of connected voids/channels which represent the dual structure of the protein; we then hydrated the identified channels using our water placement program Dowser++. Many theoretical water molecules found in the channels perfectly match the observed experimental water molecules in the structure; some other predicted water molecules have not been resolved in the experiments. The channels are of varying cross-section. Some channels are big enough to accommodate water molecules that are suitable to conduct protons; others are too narrow to hold water but require only minor conformational changes to accommodate proton transfer. We provide a preliminary analysis of proton conductivity of the network channels, classifying the proton transfer channels as open, closed, and partially open, and discuss possible conformational changes that can modulate, i.e. open and close, the channels.
    Keywords:  Complex I; Dowser++; Electron Transport Chain; proton channels; proton pumping; proton transfer; water in proteins
    DOI:  https://doi.org/10.1016/j.bpj.2024.07.041
  14. J Proteome Res. 2024 Jul 30.
    FAS Inhibited Proteomics and Phosphoproteomics Profiling of Colorectal Cancer Spheroids Shows Activation of Ferroptotic Death Mechanism.
    Brian D Fries, Amanda B Hummon.
      Colorectal cancer (CRC) is projected to become the third most diagnosed and third most fatal cancer in the United States by 2024, with early onset CRC on the rise. Research is constantly underway to discover novel therapeutics for the treatment of various cancers to improve patient outcomes and survival. Fatty acid synthase (FAS) has become a druggable target of interest for the treatment of many different cancers. One such inhibitor, TVB-2640, has gained popularity for its high specificity for FAS and has entered a phase 1 clinical trial for the treatment of solid tumors. However, the distinct molecular differences that occur upon inhibition of FAS have yet to be understood. Here, we conduct proteomics and phosphoproteomics analyses on HCT 116 and HT-29 CRC spheroids inhibited with either a generation 1 (cerulenin) or generation 2 (TVB-2640) FAS inhibitor. Proteins involved in lipid metabolism and cellular respiration were altered in abundance. It was also observed that proteins involved in ferroptosis─an iron mediated form of cell death─were altered. These results show that HT-29 spheroids exposed to cerulenin or TVB-2640 are undergoing a ferroptotic death mechanism. The data were deposited to the ProteomeXchange Consortium via the PRIDE repository with the identifier PXD050987.
    Keywords:  cancer; colorectal cancer; data-independent acquisition; mass spectrometry; phosphoproteomics; proteomics; spheroids
    DOI:  https://doi.org/10.1021/acs.jproteome.4c00252
  15. Cytometry A. 2024 Jul 30.
    AutoMitoNetwork: Software for analyzing mitochondrial networks in autofluorescence images to enable label-free cell classification.
    Shannon Handley, Ayad G Anwer, Aline Knab, Akanksha Bhargava, Ewa M Goldys.
      High-resolution mitochondria imaging in combination with image analysis tools have significantly advanced our understanding of cellular function in health and disease. However, most image analysis tools for mitochondrial studies have been designed to work with fluorescently labeled images only. Additionally, efforts to integrate features describing mitochondrial networks with machine learning techniques for the differentiation of cell types have been limited. Herein, we present AutoMitoNetwork software for image-based assessment of mitochondrial networks in label-free autofluorescence images using a range of interpretable morphological, intensity, and textural features. To demonstrate its utility, we characterized unstained mitochondrial networks in healthy retinal cells and in retinal cells exposed to two types of treatments: rotenone, which directly inhibited mitochondrial respiration and ATP production, and iodoacetic acid, which had a milder impact on mitochondrial networks via the inhibition of anaerobic glycolysis. For both cases, our multi-dimensional feature analysis combined with a support vector machine classifier distinguished between healthy cells and those treated with rotenone or iodoacetic acid. Subtle changes in morphological features were measured including increased fragmentation in the treated retinal cells, pointing to an association with metabolic mechanisms. AutoMitoNetwork opens new options for image-based machine learning in label-free imaging, diagnostics, and mitochondrial disease drug development.
    Keywords:  autofluorescence; biological image analysis; label‐free imaging; machine learning; mitochondria; mitochondria network
    DOI:  https://doi.org/10.1002/cyto.a.24889
This page is being maintained by Thomas Krichel. It was last updated on 2024‒08‒04 at 0:59.