bims-mecosi 2024-09-08 papers

Issue of 2024–09–08
seven papers selected by
Verena Kohler, Umeå University

Pharmacol Res. 2024 Sep 02. pii: S1043-6618(24)00338-4. [Epub ahead of print]208 107393

F-ATP synthase inhibitory factor 1 and mitochondria-organelle interactions: New insight and implications.

Mitochondria are metabolic hub, and act as primary sites for reactive oxygen species (ROS) and metabolites generation. Mitochondrial Ca2+ uptake contributes to Ca2+ storage. Mitochondria-organelle interactions are important for cellular metabolic adaptation, biosynthesis, redox balance, cell fate. Organelle communications are mediated by Ca2+/ROS signals, vesicle transport and membrane contact sites. The permeability transition pore (PTP) is an unselective channel that provides a release pathway for Ca2+/ROS, mtDNA and metabolites. F-ATP synthase inhibitory factor 1 (IF1) participates in regulation of PTP opening and is required for the translocation of transcriptional factors c-Myc/PGC1α to mitochondria to stimulate metabolic switch. IF1, a mitochondrial specific protein, has been suggested to regulate other organelles including nucleus, endoplasmic reticulum and lysosomes. IF1 may be able to mediate mitochondria-organelle interactions and cellular physiology through regulation of PTP activity.

Keywords: Ca(2+); F-ATP synthase inhibitory factor 1; Metabolites; Mitochondria; Mitochondria-organelle interactions; Permeability transition; ROS

DOI: https://doi.org/10.1016/j.phrs.2024.107393

J Microsc. 2024 Aug 30.

The mutual influence of microtubules and the cortical ER on their coordinated organisation.

Lalita Pal, Eduard Belausov, Vikas Dwivedi, Sela Yechezkel, Einat Sadot.

The endoplasmic reticulum (ER) is the largest organelle in terms of membrane content, occupying the entire cytoplasmic volume. It is tethered to the cell cortex through ER-plasma membrane contact sites (EPCS). Previous studies have shown that EPCSs labelled by VAP27 align with cortical microtubules, and that ER tubules elongate along microtubules. Here, we addressed the question whether this relationship is bidirectional, with EPCSs influencing microtubule organisation. Using TIRF microscopy to track EPCSs and microtubule dynamics simultaneously, we demonstrate that while EPCSs remain stable, microtubules are highly dynamic and can adjust their positioning based on nearby EPCS in Arabidopsis cotyledon epidermis. In lobes of epidermal cells enclosed by two indentations, where microtubules bundle together, EPCSs flank the bundles and exhibit a distinctive arrangement, forming symmetric arcs in relation to the lobe axis. In guard cells, transversely oriented ER tubules co-align with microtubules. Disrupting microtubules with the drug oryzalin leads to transient guard cells-ER remodelling, followed by its reorganisation into transverse tubules before microtubule recovery. Taken together our observations suggest, that the positioning of EPCSs and cortical microtubules, can affect each other and the organisation of cortical ER.

Keywords: EPCS; cortical microtubules; epidermal cells; guard cells

DOI: https://doi.org/10.1111/jmi.13356

Aging Dis. 2024 Aug 22.

Mitochondria-Associated Membranes in Aging and Senescence.

Zhaojia Wang, Xiao Du, Shiran Yu, Xuzhen Yan, Yanguo Xin.

Although the pursuit of eternal youth remains elusive, progress in the fields of medicine and science has greatly extended the human lifespan. Nevertheless, the rising incidence of diseases and their economic impact present notable obstacles. Mitochondria-associated membranes (MAMs), essential sites for close interaction between mitochondria and the endoplasmic reticulum (ER), are increasingly recognized for their involvement in both normal cellular processes and the development of diseases. Studies suggest that MAMs undergo dynamic alterations, particularly pertinent in the investigation of age-related illnesses. This review highlights the significance of MAMs in age-related conditions, elucidating the morphological and functional alterations in mitochondria and ER during aging. By emphasizing the complex interaction between these organelles, it demonstrates the cell's adaptive responses to combat age-related deterioration. Suggesting MAMs as potential targets for therapeutic interventions holds the potential for attenuating the progression of age-related diseases.

DOI: https://doi.org/10.14336/AD.2024.0652

Adv Physiol Educ. 2024 Sep 05.

A Workshop to Enrich Physiological Understanding Through Hands-On Learning About Mitochondria-Endoplasmic Reticulum Contact Sites.

Physiology is an important field for students to gain a better understanding of biological mechanisms. Yet, many students often find it difficult to learn from lectures, resulting in poor retention. Here, we focus on the utilization of a learning workshop model to teach students at different levels ranging from middle school to undergraduate. We specifically designed a workshop to teach students about mitochondria endoplasmic reticulum contact (MERC) sites. The workshop was implemented for middle-school students in a laboratory setting that incorporated a pre-test to gauge prior knowledge, instructional time, hands-on activities, interactive learning from experts, and a post-test. We observed that the students remained engaged during the session relied on interactive methods, teamed with their peers to complete tasks, and delighted in the experience. Implications for the design of future physiological workshops are further offered.

Keywords: Blended Learning; Mitochondria; STEMM Education Workshops; Underrepresented

DOI: https://doi.org/10.1152/advan.00271.2023

J Cell Sci. 2024 Sep 06. pii: jcs.262347. [Epub ahead of print]

Fission yeast Duc1 links to ER-PM contact sites and influences PM lipid composition and cytokinetic ring anchoring.

Alaina H Willet, Joshua S Park, Chloe E Snider, Jingdian Jamie Huang, Jun-Song Chen, Kathleen L Gould.

Cytokinesis is the final stage of the cell cycle that results in the physical separation of daughter cells. To accomplish cytokinesis, many organisms build an actin- and myosin-based cytokinetic ring (CR) anchored to the plasma membrane (PM). Defects in CR-PM anchoring can arise when the PM lipid, phosphatidylinositol-4,5- bisphosphate [PI(4,5)P2], is depleted. In Schizosaccharomyces pombe, reduced PM PI(4,5)P2 results in a CR that cannot maintain its medial position and slides toward one cell end, resulting in two differently sized daughter cells. S. pombe PM PI(4,5)P2 is synthesized by the PI5-kinase Its3, but what regulates this enzyme to maintain appropriate PM PI(4,5)P2 levels is not known in S. pombe. To identify Its3 regulators, we used proximity-based biotinylation and the uncharacterized protein Duc1 was specifically detected. We discovered that Duc1 decorates the PM except at the cell division site and that its unique localization pattern is dictated by binding to the ER-PM contact site proteins, Scs2 and Scs22. Our evidence suggests Duc1 also binds PI(4,5)P2 and helps enrich Its3 at the lateral PM, thereby promoting PM PI(4,5)P2 synthesis and robust CR-PM anchoring.

Keywords: Cytokinesis; Cytokinetic ring; ER-PM; Fission yeast; PI(4,5)P2; PI5-kinase

DOI: https://doi.org/10.1242/jcs.262347

Contact (Thousand Oaks). 2024 Jan-Dec;7:7 25152564241273598

Getting to Grips with the Oxysterol-Binding Protein Family - a Forty Year Perspective.

Vesa M Olkkonen, Elina Ikonen.

This review discusses how research around the oxysterol-binding protein family has evolved. We briefly summarize how this protein family, designated OSBP-related (ORP) or OSBP-like (OSBPL) proteins, was discovered, how protein domains highly conserved among family members between taxa paved the way for understanding their mechanisms of action, and how insights into protein structural and functional features help to understand their versatility as lipid transporters. We also discuss questions and future avenues of research opened by these findings. The investigations on oxysterol-binding protein family serve as a real-life example of the notion that science often advances as a collective effort of multiple lines of enquiry, including serendipitous routes. While original articles invariably explain the motivation of the research undertaken in rational terms, the actual paths to findings may be less intentional. Fortunately, this does not reduce the impact of the discoveries made. Besides hopefully providing a useful account of ORP family proteins, we aim to convey this message.

Keywords: OSBP; lipid transfer protein; lipid transport; membrane contact site; protein family

DOI: https://doi.org/10.1177/25152564241273598

Biochim Biophys Acta Mol Basis Dis. 2024 Aug 30. pii: S0925-4439(24)00474-5. [Epub ahead of print]1870(8): 167480

Electroacupuncture pretreatment maintains mitochondrial quality control via HO-1/MIC60 signaling pathway to alleviate endotoxin-induced acute lung injury.

Jia Shi, Meiling Piao, Chuanning Liu, Jing Yang, Xin Guan, Huayang Liu, Qiujia Li, Yuan Zhang, Jianbo Yu.

Electroacupuncture has been demonstrated to mitigate endotoxin-induced acute lung injury by enhancing mitochondrial function. This study investigates whether electroacupuncture confers lung protection through the regulation of mitochondrial quality control mediated by heme oxygenase-1 (HO-1) and the mitochondrial inner membrane protein MIC60. HO-1, an inducible stress protein, is crucial for maintaining mitochondrial homeostasis and protecting against lung injury. MIC60, a key component of the mitochondrial contact site and cristae organizing system, supports mitochondrial integrity. We employed genetic knockout/silencing and cell transfection techniques to model lipopolysaccharide (LPS)-induced lung injury, assessing changes in mitochondrial structure, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and the expression of proteins essential for mitochondrial quality control. Our findings reveal that electroacupuncture alleviates endotoxin-induced acute lung injury and associated mitochondrial dysfunction, as evidenced by reductions in lung injury scores, decreased ROS production, and suppressed expression of proteins involved in mitochondrial fission and mitophagy. Additionally, electroacupuncture enhanced MMP and upregulated proteins that facilitate mitochondrial fusion and biogenesis. Importantly, the protective effects of electroacupuncture were reduced in models with Hmox1 knockout or Mic60 silencing, and in macrophages transfected with Hmox1-siRNA or Mic60-siRNA. Moreover, HO-1 was found to influence MIC60 expression during electroacupuncture preconditioning and LPS challenge, demonstrating that these proteins not only co-localize but also interact directly. In conclusion, electroacupuncture effectively modulates mitochondrial quality control through the HO-1/MIC60 signaling pathway, offering an adjunctive therapeutic strategy to ameliorate endotoxin-induced acute lung injury in both in vivo and in vitro settings.

Keywords: Acute lung injury; Electroacupuncture; Endotoxemia; Heme oxygenase-1; MIC60/mitofilin; Mitochondrial quality control

DOI: https://doi.org/10.1016/j.bbadis.2024.167480