bims-midtic 2023-10-08 papers

bims-midtic

Biomed News

on Mitochondrial dynamics and trafficking in cells

Issue of 2023‒10‒08
fourteen papers selected by
Omkar Joshi, Turku Bioscience

Alternate splice variants of the mitochondrial fission protein DNM1L/Drp1 regulate mitochondrial dynamics and cell fate in ovarian cancer.
A conserved, non-canonical insert in FIS1 mediates TBC1D15 and DRP1 recruitment for mitochondrial fission.
Syntaxin 17 Protects Against Heart Failure Through Recruitment of CDK1 to Promote DRP1-Dependent Mitophagy.
Mitophagy for cardioprotection.
Mitochondrial transfer in hematological malignancies.
Zika virus modulates mitochondrial dynamics, mitophagy, and mitochondria-derived vesicles to facilitate viral replication in trophoblast cells.
Inter-organellar nucleic acid communication by a mitochondrial tRNA regulates nuclear metabolic transcription.
Caveolin-1 Autonomously Regulates Hippocampal Neurogenesis Via Mitochondrial Dynamics.
Broadening horizons: the contribution of mitochondria-associated endoplasmic reticulum membrane (MAM) dysfunction in diabetic kidney disease.
KDM5-mediated activation of genes required for mitochondrial biology is necessary for viability in Drosophila.
Complementary Approaches to Interrogate Mitophagy Flux in Pancreatic β-Cells.
PGC1-α-driven mitochondrial biogenesis contributes to a cancer stem cell phenotype in melanoma.
Mitochondrial Membrane Model: Lipids, Elastic Properties and the Changing Curvature of Cardiolipin.
A Mitochondrial Nanoguard Modulates Redox Homeostasis and Bioenergy Metabolism in Diabetic Peripheral Neuropathy.

bioRxiv. 2023 Sep 20. pii: 2023.09.20.558501. [Epub ahead of print]

Alternate splice variants of the mitochondrial fission protein DNM1L/Drp1 regulate mitochondrial dynamics and cell fate in ovarian cancer.

Zaineb Javed, Dong Hui Shin, Weihua Pan, Sierra R White, Yeon Soo Kim, Amal Taher Elhaw, Shriya Kamlapurkar, Ya-Yun Cheng, J Cory Benson, Ahmed Emam Abdelnaby, Rebecca Phaeton, Hong-Gang Wang, Shengyu Yang, Mara Lisa Grove Sullivan, Simon C Watkins, Steven J Mullett, Stacy Lynn Gelhaus, Nam Y Lee, Lan Coffman, Katherine Marie Aird, Mohamed Trebak, Mythreye Karthikeyan, Vonn Walter, Nadine Hempel.

Aberrant mitochondrial fission/fusion dynamics have previously been reported in cancer cells. While post translational modifications are known regulators of GTPases of the mitochondrial fission/fusion machinery, we show for the first time that alternate splice variants of the fission protein Drp1 (DNM1L) have specific and unique roles in ovarian cancer, adding to the complexity of mitochondrial fission/fusion regulation in tumor cells. We find that ovarian cancer specimens express a Drp1 alternate splice transcript variant lacking exon 16 of the variable domain. High expression of Drp1 lacking exon 16 relative to other transcripts is associated with poor patient outcome. Unlike the unspliced variant, expression of Drp1 lacking exon 16 leads to decreased association of Drp1 to mitochondrial fission sites, more fused mitochondrial networks, enhanced respiration and TCA cycle metabolites, and is associated with a more tumorigenic phenotype. These effects can also be reversed by specific siRNA-mediated inhibition of the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the significance of the pathophysiological consequences of Drp1 alternate splicing and divergent functions of Drp1 splice variants, and strongly warrant consideration of Drp1 splicing in future studies.

DOI: https://doi.org/10.1101/2023.09.20.558501
J Biol Chem. 2023 Sep 28. pii: S0021-9258(23)02331-1. [Epub ahead of print] 105303

A conserved, non-canonical insert in FIS1 mediates TBC1D15 and DRP1 recruitment for mitochondrial fission.

Ugochukwu K Ihenacho, Rafael Toro, Rana H Mansour, R Blake Hill.

  Mitochondrial fission protein 1 (FIS1) is conserved in all eukaryotes, yet its function in metazoans is thought divergent from lower eukaryotes like fungi. To address this discrepancy, structure-based sequence alignments revealed a conserved but non-canonical three-residue insert (Ser-X-X) in a turn of FIS1, suggesting a conserved function. In vertebrate FIS1, this insert is serine (S45), lysine (K46), and tyrosine (Y47). To determine the biological role of the "SKY insert" in vertebrates, three variants were evaluated for their fold and tested in HCT116 cells for altered mitochondrial morphology and recruitment of effectors, DRP1 and TBC1D15. Substitution of the SKY insert with three alanine residues (AAA) or deletion of the insert (ΔSKY) did not substantially alter the fold or thermal stability of the protein. Replacing SKY with a canonical turn (ΔSKYD49G) introduced significant conformational heterogeneity by NMR that was removed upon deletion of a known regulatory region, the FIS1 arm. Expression of AAA fragmented mitochondria into perinuclear clumps associated with increased mitochondrial DRP1 similar to the wild-type protein. In contrast, the expression of ΔSKY variants led to elongated mitochondrial networks and reduced mitochondrial DRP1 by colocalization analysis, although DRP1 coimmunoprecipitates were highly enriched with ΔSKY variants. Co-expression of YFP-TBC1D15 with ΔSKY variants rescued mitochondrial morphology, despite a reduced ability to drive YFP-TBC1D15 into punctate structures that is found upon co-expression with wildtype FIS1 or the AAA variant. In support YFP-TBC1D15 coimmunoprecipitates were poorly enriched with ΔSKY variants. Co-expression of YFP-TBC1D15 also revealed a gain of function phenotype with the AAA variant compared to wildtype. Collectively these results show that FIS1 can be modulated by conserved residues, thus supporting a unifying model whereby FIS1 activity is effectively governed by intramolecular interactions between the regulatory FIS1 arm and an S-X-X insert that is conserved across eukaryotes.

Keywords:  Mitochondria; dynamin; fission; mitophagy; nuclear magnetic resonance (NMR); organelle dynamic; peroxisome; protein motif; repeat proteins; tetratricopeptide repeat

DOI:  https://doi.org/10.1016/j.jbc.2023.105303
JACC Basic Transl Sci. 2023 Sep;8(9): 1215-1239

Syntaxin 17 Protects Against Heart Failure Through Recruitment of CDK1 to Promote DRP1-Dependent Mitophagy.

Haixia Xu, Xiang Wang, Wenjun Yu, Shiqun Sun, Ne N Wu, Junbo Ge, Jun Ren, Yingmei Zhang.

  Mitochondrial dysfunction is suggested to be a major contributor for the progression of heart failure (HF). Here we examined the role of syntaxin 17 (STX17) in the progression of HF. Cardiac-specific Stx17 knockout manifested cardiac dysfunction and mitochondrial damage, associated with reduced levels of p(S616)-dynamin-related protein 1 (DRP1) in mitochondria-associated endoplasmic reticulum membranes and dampened mitophagy. Cardiac STX17 overexpression promoted DRP1-dependent mitophagy and attenuated transverse aortic constriction-induced contractile and mitochondrial damage. Furthermore, STX17 recruited cyclin-dependent kinase-1 through its SNARE domain onto mitochondria-associated endoplasmic reticulum membranes, to phosphorylate DRP1 at Ser616 and promote DRP1-mediated mitophagy upon transverse aortic constriction stress. These findings indicate the potential therapeutic benefit of targeting STX17 in the mitigation of HF.

Keywords:  CDK1; DRP1; MAMs; STX17; mitophagy; pressure overload–induced heart failure

DOI:  https://doi.org/10.1016/j.jacbts.2023.04.006
Basic Res Cardiol. 2023 Oct 05. 118(1): 42

Mitophagy for cardioprotection.

Allen Sam Titus, Eun-Ah Sung, Daniela Zablocki, Junichi Sadoshima.

  Mitochondrial function is maintained by several strictly coordinated mechanisms, collectively termed mitochondrial quality control mechanisms, including fusion and fission, degradation, and biogenesis. As the primary source of energy in cardiomyocytes, mitochondria are the central organelle for maintaining cardiac function. Since adult cardiomyocytes in humans rarely divide, the number of dysfunctional mitochondria cannot easily be diluted through cell division. Thus, efficient degradation of dysfunctional mitochondria is crucial to maintaining cellular function. Mitophagy, a mitochondria specific form of autophagy, is a major mechanism by which damaged or unnecessary mitochondria are targeted and eliminated. Mitophagy is active in cardiomyocytes at baseline and in response to stress, and plays an essential role in maintaining the quality of mitochondria in cardiomyocytes. Mitophagy is mediated through multiple mechanisms in the heart, and each of these mechanisms can partially compensate for the loss of another mechanism. However, insufficient levels of mitophagy eventually lead to mitochondrial dysfunction and the development of heart failure. In this review, we discuss the molecular mechanisms of mitophagy in the heart and the role of mitophagy in cardiac pathophysiology, with the focus on recent findings in the field.

Keywords:  Alternative mitophagy; Drp1; Mitochondrial quality control; Mitophagy

DOI:  https://doi.org/10.1007/s00395-023-01009-x
Biomark Res. 2023 Oct 05. 11(1): 89

Mitochondrial transfer in hematological malignancies.

Xiaodong Guo, Can Can, Wancheng Liu, Yihong Wei, Xinyu Yang, Jinting Liu, Hexiao Jia, Wenbo Jia, Hanyang Wu, Daoxin Ma.

  Mitochondria are energy-generated organelles and take an important part in biological metabolism. Mitochondria could be transferred between cells, which serves as a new intercellular communication. Mitochondrial transfer improves mitochondrial defects, restores the biological functions of recipient cells, and maintains the high metabolic requirements of tumor cells as well as drug resistance. In recent years, it has been reported mitochondrial transfer between cells of bone marrow microenvironment and hematological malignant cells play a critical role in the disease progression and resistance during chemotherapy. In this review, we discuss the patterns and mechanisms on mitochondrial transfer and their engagement in different pathophysiological contexts and outline the latest knowledge on intercellular transport of mitochondria in hematological malignancies. Besides, we briefly outline the drug resistance mechanisms caused by mitochondrial transfer in cells during chemotherapy. Our review demonstrates a theoretical basis for mitochondrial transfer as a prospective therapeutic target to increase the treatment efficiency in hematological malignancies and improve the prognosis of patients.

Keywords:  Extracellular mitochondria; Extracellular vesicles; Hematological malignancies; Mitochondrial transfer; Tunneling nanotubes

DOI:  https://doi.org/10.1186/s40364-023-00529-x
Front Immunol. 2023 ;14 1203645

Zika virus modulates mitochondrial dynamics, mitophagy, and mitochondria-derived vesicles to facilitate viral replication in trophoblast cells.

Jae Kyung Lee, Ok Sarah Shin.

  Zika virus (ZIKV) remains a global public health threat with the potential risk of a future outbreak. Since viral infections are known to exploit mitochondria-mediated cellular processes, we investigated the effects of ZIKV infection in trophoblast cells in terms of the different mitochondrial quality control pathways that govern mitochondrial integrity and function. Here we demonstrate that ZIKV (PRVABC59) infection of JEG-3 trophoblast cells manipulates mitochondrial dynamics, mitophagy, and formation of mitochondria-derived vesicles (MDVs). Specifically, ZIKV nonstructural protein 4A (NS4A) translocates to the mitochondria, triggers mitochondrial fission and mitophagy, and suppresses mitochondrial associated antiviral protein (MAVS)-mediated type I interferon (IFN) response. Furthermore, proteomics profiling of small extracellular vesicles (sEVs) revealed an enrichment of mitochondrial proteins in sEVs secreted by ZIKV-infected JEG-3 cells, suggesting that MDV formation may also be another mitochondrial quality control mechanism manipulated during placental ZIKV infection. Altogether, our findings highlight the different mitochondrial quality control mechanisms manipulated by ZIKV during infection of placental cells as host immune evasion mechanisms utilized by ZIKV at the placenta to suppress the host antiviral response and facilitate viral infection.

Keywords:  mitochondria-derived vesicles (MDVs); mitochondrial quality control; mitophagy; nonstructural protein 4A (NS4A); zika virus (ZIKV)

DOI:  https://doi.org/10.3389/fimmu.2023.1203645
bioRxiv. 2023 Sep 22. pii: 2023.09.21.558912. [Epub ahead of print]

Inter-organellar nucleic acid communication by a mitochondrial tRNA regulates nuclear metabolic transcription.

Christopher Rouya, King Faisal Yambire, Mark L Derbyshire, Hanan Alwaseem, Sohail F Tavazoie.

Efficient communication between mitochondria and the nucleus underlies homoeostatic metabolic control, though the involved mitochondrial factors and their mechanisms are poorly defined. Here, we report the surprising detection of multiple mitochondrial-derived transfer RNAs (mito-tRNAs) within the nuclei of human cells. Focused studies of nuclear-transported mito-tRNA-asparagine (mtAsn) revealed that its cognate charging enzyme (NARS2) is also present in the nucleus. MtAsn promoted interaction of NARS2 with histone deacetylase 2 (HDAC2), and repressed HDAC2 association with specific chromatin loci. Perturbation of this axis using antisense oligonucleotides promoted nucleotide biogenesis and enhanced breast cancer growth, and RNA and nascent transcript sequencing demonstrated specific alterations in the transcription of nuclear genes. These findings uncover nucleic-acid mediated communication between two organelles and the existence of a machinery for nuclear gene regulation by a mito-tRNA that restricts tumor growth through metabolic control.Highlights: Multiple mitochondrial-derived tRNAs are detected in human cell nucleiMtAsn promotes binding between NARS2 and HDAC2Metabolic alterations driven by mtAsn impact cell proliferationMtAsn inhibition releases HDAC2 to bind and transcriptionally regulate multiple nuclear genes.

DOI: https://doi.org/10.1101/2023.09.21.558912
bioRxiv. 2023 Sep 24. pii: 2023.09.23.558792. [Epub ahead of print]

Caveolin-1 Autonomously Regulates Hippocampal Neurogenesis Via Mitochondrial Dynamics.

Terilyn K L Stephen, Luis Aponte Cofresi, Elvis Quiroz, Kofi Owusu-Ansah, Yomna Ibrahim, Ellis Qualls, Jeffery Marshall, Wenping Li, Aashutosh Shetti, Jacqueline A Bonds, Richard D Minshall, Stephanie M Cologna, Orly Lazarov.

The mechanisms underlying adult hippocampal neurogenesis (AHN) are not fully understood. AHN plays instrumental roles in learning and memory. Understanding the signals that regulate AHN has implications for brain function and therapy. Here we show that Caveolin-1 (Cav-1), a protein that is highly enriched in endothelial cells and the principal component of caveolae, autonomously regulates AHN. Conditional deletion of Cav-1 in adult neural progenitor cells (nestin +) led to increased neurogenesis and enhanced performance of mice in contextual discrimination. Proteomic analysis revealed that Cav-1 plays a role in mitochondrial pathways in neural progenitor cells. Importantly, Cav-1 was localized to the mitochondria in neural progenitor cells and modulated mitochondrial fission-fusion, a critical process in neurogenesis. These results suggest that Cav-1 is a novel regulator of AHN and underscore the impact of AHN on cognition.

DOI: https://doi.org/10.1101/2023.09.23.558792
Int J Biol Sci. 2023 ;19(14): 4427-4441

Broadening horizons: the contribution of mitochondria-associated endoplasmic reticulum membrane (MAM) dysfunction in diabetic kidney disease.

Yong Liu, Yingjin Qiao, Shaokang Pan, Jingfang Chen, Zihui Mao, Kaidi Ren, Yang Yang, Qi Feng, Dongwei Liu, Zhangsuo Liu.

  Diabetic kidney disease (DKD) is a global health issue that presents a complex pathogenesis and limited treatment options. To provide guidance for precise therapies, it is crucial to accurately identify the pathogenesis of DKD. Several studies have recognized that mitochondrial and endoplasmic reticulum (ER) dysfunction are key drivers of the pathogenesis of DKD. The mitochondria-associated ER membrane (MAM) is a dynamic membrane contact site (MSC) that connects the ER and mitochondria and is essential in maintaining the normal function of the two organelles. MAM is involved in various cellular processes, including lipid synthesis and transport, calcium homeostasis, mitochondrial fusion and fission, and ER stress. Meanwhile, recent studies confirm that MAM plays a significant role in the pathogenesis of DKD by regulating glucose metabolism, lipid metabolism, inflammation, ER stress, mitochondrial fission and fusion, and autophagy. Herein, this review aims to provide a comprehensive summary of the physiological function of MAMs and their impact on the progression of DKD. Subsequently, we discuss the trend of pharmaceutical studies that target MAM resident proteins for treating DKD. Furthermore, we also explore the future development prospects of MAM in DKD research, thereby providing a new perspective for basic studies and clinical treatment of DKD.

Keywords:  Mitochondria-associated endoplasmic reticulum membrane (MAM); calcium homeostasis; diabetic kidney disease (DKD); lipid metabolism; mitochondrial physiology

DOI:  https://doi.org/10.7150/ijbs.86608
Development. 2023 Oct 06. pii: dev.202024. [Epub ahead of print]

KDM5-mediated activation of genes required for mitochondrial biology is necessary for viability in Drosophila.

Michael F Rogers, Owen J Marshall, Julie Secombe.

  Histone modifying proteins play critical roles in the precise regulation of the transcriptional programs that coordinate development. KDM5 family proteins interact with chromatin through demethylating H3K4me3 as well as demethylase-independent mechanisms that remain less understood. To gain fundamental insights into the transcriptional activities of KDM5 proteins, we examined the essential roles of the single kdm5 ortholog of Drosophila during development. KDM5 performs critical functions in the larval neuroendocrine prothoracic gland, providing a model to define its role in regulating key gene expression programs. Integrating genome binding and transcriptomic data, we identify that KDM5 regulates the expression of genes critical for the function and maintenance of mitochondria, and we find that loss of KDM5 causes morphological changes to mitochondria. This is key to the developmental functions of KDM5, as expression of the mitochondrial biogenesis transcription factor Ets97D, homolog of GABPα, is able to suppress the altered mitochondrial morphology as well as the lethality of kdm5 null animals. Together, these data establish KDM5-mediated cellular functions that are important for normal development and could contribute to KDM5-linked disorders when dysregulated.

Keywords:  Demethylase; KDM5; Mitochondria; Prothoracic gland; Transcription

DOI:  https://doi.org/10.1242/dev.202024
J Vis Exp. 2023 09 15.

Complementary Approaches to Interrogate Mitophagy Flux in Pancreatic β-Cells.

Elena Levi-D'Ancona, Vaibhav Sidarala, Scott A Soleimanpour.

Mitophagy is a quality control mechanism necessary to maintain optimal mitochondrial function. Dysfunctional β-cell mitophagy results in insufficient insulin release. Advanced quantitative assessments of mitophagy often require the use of genetic reporters. The mt-Keima mouse model, which expresses a mitochondria-targeted pH-sensitive dual-excitation ratiometric probe for quantifying mitophagy via flow cytometry, has been optimized in β-cells. The ratio of acidic-to-neutral mt-Keima wavelength emissions can be used to robustly quantify mitophagy. However, using genetic mitophagy reporters can be challenging when working with complex genetic mouse models or difficult-to-transfect cells, such as primary human islets. This protocol describes a novel complementary dye-based method to quantify β-cell mitophagy in primary islets using MtPhagy. MtPhagy is a pH-sensitive, cell-permeable dye that accumulates in the mitochondria and increases its fluorescence intensity when mitochondria are in low pH environments, such as lysosomes during mitophagy. By combining the MtPhagy dye with Fluozin-3-AM, a Zn2+ indicator that selects for β-cells, and Tetramethylrhodamine, ethyl ester (TMRE) to assess mitochondrial membrane potential, mitophagy flux can be quantified specifically in β-cells via flow cytometry. These two approaches are highly complementary, allowing for flexibility and precision in assessing mitochondrial quality control in numerous β-cell models.

DOI: https://doi.org/10.3791/65789
Biochim Biophys Acta Mol Basis Dis. 2023 Sep 25. pii: S0925-4439(23)00263-6. [Epub ahead of print]1870(1): 166897

PGC1-α-driven mitochondrial biogenesis contributes to a cancer stem cell phenotype in melanoma.

Fabrizio Fontana, Chiara Macchi, Martina Anselmi, Alessandra Stefania Rizzuto, Massimiliano Ruscica, Patrizia Limonta.

  Little is known about the metabolic regulation of cancer stem cells (CSCs) in melanoma. Here, we used A375 and WM115 cell lines to dissect the role of mitochondria in conferring CSC traits. Notably, we observed that A375 and WM115 melanospheres, known to be enriched in ABCG2+ CSCs, showed higher mitochondrial mass compared with their adherent counterpart. In particular, they displayed increased PGC1-α expression and oxidative phosphorylation (OXPHOS) complex levels, leading to a metabolic switch characterized by enhanced mitochondrial membrane potential, oxygen consumption, ATP synthesis and ROS production. Interestingly, PGC1-α silencing resulted in the suppression of CSC features, including clonogenic ability, migration, spheroid formation and ABCG2 enrichment. Similarly, XCT790 and SR-18292, two PGC1-α inhibitors, were able not only to reduce melanoma tumorigenicity and invasion but also to block melanosphere growth and propagation and ABCG2+ cell proliferation. In conclusion, improved mitochondrial biogenesis is associated with a stem-like phenotype in melanoma, and therapeutically targeting the mitochondria-enriched CSC subpopulation might overcome tumor progression.

Keywords:  Melanoma; Mitochondrial biogenesis; Oxidative phosphorylation (OXPHOS); PGC1-α; cancer stem cells (CSCs)

DOI:  https://doi.org/10.1016/j.bbadis.2023.166897
Biophys J. 2023 Oct 05. pii: S0006-3495(23)00626-4. [Epub ahead of print]

Mitochondrial Membrane Model: Lipids, Elastic Properties and the Changing Curvature of Cardiolipin.

Sukanya Konar, Hina Arif, Christoph Allolio.

Mammalian and Drosophila Melanogaster model mitochondrial membrane compositions are constructed from experimental data. Simplified compositions for inner and outer mitochondrial membranes are provided, including an asymmetric inner mitochondrial membrane. We performed atomistic molecular dynamics simulations of these membranes and computed their material properties. When comparing these properties to those obtained by extrapolation from their constituting lipids, we find good overall agreement. Finally, we analyzed the curvature effect of cardiolipin, considering ion concentration effects, oxidation and pH. We draw the conclusion that cardiolipin negative curvature is most likely due to counterion effects, such as cation adsorption, in particular of H3O+. This oft-neglected effect might account for the puzzling behavior of this lipid.

DOI: https://doi.org/10.1016/j.bpj.2023.10.002
ACS Nano. 2023 Oct 02.

A Mitochondrial Nanoguard Modulates Redox Homeostasis and Bioenergy Metabolism in Diabetic Peripheral Neuropathy.

Yangxue Yao, Xiaoyu Lei, Yun Wang, Geru Zhang, Hongxiao Huang, Yuxuan Zhao, Sirong Shi, Yang Gao, Xiaoxiao Cai, Shaojingya Gao, Yunfeng Lin.

  As a major late complication of diabetes, diabetic peripheral neuropathy (DPN) is the primary reason for amputation. Nevertheless, there are no wonder drugs available. Regulating dysfunctional mitochondria is a key therapeutic target for DPN. Resveratrol (RSV) is widely proven to guard mitochondria, yet the unsatisfactory bioavailability restricts its clinical application. Tetrahedral framework nucleic acids (tFNAs) are promising carriers due to their excellent cell entrance efficiency, biological safety, and structure editability. Here, RSV was intercalated into tFNAs to form the tFNAs-RSV complexes. tFNAs-RSV achieved enhanced stability, bioavailability, and biocompatibility compared with tFNAs and RSV alone. With its treatment, reactive oxygen species (ROS) production was minimized and reductases were activated in an in vitro model of DPN. Besides, respiratory function and adenosine triphosphate (ATP) production were enhanced. tFNAs-RSV also exhibited favorable therapeutic effects on sensory dysfunction, neurovascular deterioration, demyelination, and neuroapoptosis in DPN mice. Metabolomics analysis revealed that redox regulation and energy metabolism were two principal mechanisms that were impacted during the process. Comprehensive inspections indicated that tFNAs-RSV inhibited nitrosation and oxidation and activated reductase and respiratory chain. In sum, tFNAs-RSV served as a mitochondrial nanoguard (mito-guard), representing a viable drilling target for clinical drug development of DPN.

Keywords:  bioenergy metabolism; diabetic peripheral neuropathy; mitochondria; redox homeostasis; resveratrol; tetrahedral framework nucleic acids

DOI:  https://doi.org/10.1021/acsnano.3c04462