bims-midtic Biomed News
on Mitochondrial dynamics and trafficking in cells
Issue of 2023‒12‒10
fourteen papers selected by
Omkar Joshi, Turku Bioscience
  1. The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.
  2. A new role for phosphoinositides in regulating mitochondrial dynamics.
  3. The mitochondrial fission protein DRP1 influences memory CD8+ T cell formation and function.
  4. Mitochondrial dynamics and metabolism across skin cells: implications for skin homeostasis and aging.
  5. Collective mitochondrial dynamics resolve conflicting cellular tensions: From plants to general principles.
  6. Dynamics of mitochondrial membranes under photo-oxidative stress with high spatiotemporal resolution.
  7. Apolipoproteins L1 and L3 control mitochondrial membrane dynamics.
  8. Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis.
  9. The Footprints of Mitochondrial Fission and Apoptosis in Fluoride-Induced Renal Dysfunction.
  10. Mitonuclear interactions modulate nutritional preference.
  11. Upregulation of UHRF1 Promotes PINK1-mediated Mitophagy to Alleviates Ferroptosis in Diabetic Nephropathy.
  12. Role of Pink1-mediated mitophagy in adenomyosis.
  13. Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity.
  14. RTA 408 ameliorates diabetic cardiomyopathy by activating Nrf2 to regulate mitochondrial fission and fusion and inhibiting NF-κB-mediated inflammation.
  1. Cell Cycle. 2023 Dec 05. 1-19
    The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.
    Nian-Siou Wu, I-Chu Ma, Yi-Fan Lin, Huey-Jiun Ko, Joon-Khim Loh, Yi-Ren Hong.
      Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson's disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design.
    Keywords:  Drp1; Mitochondrial Adaptors; cell cycle; mitophagy; phosphorylation
    DOI:  https://doi.org/10.1080/15384101.2023.2289753
  2. Adv Biol Regul. 2023 Nov 30. pii: S2212-4926(23)00047-7. [Epub ahead of print] 101001
    A new role for phosphoinositides in regulating mitochondrial dynamics.
    Sonia Raveena Lourdes, Rajendra Gurung, Saveen Giri, Christina A Mitchell, Meagan J McGrath.
      Phosphoinositides are a minor group of membrane-associated phospholipids that are transiently generated on the cytoplasmic leaflet of many organelle membranes and the plasma membrane. There are seven functionally distinct phosphoinositides, each derived via the reversible phosphorylation of phosphatidylinositol in various combinations on the inositol ring. Their generation and termination is tightly regulated by phosphatidylinositol-kinases and -phosphatases. These enzymes can function together in an integrated and coordinated manner, whereby the phosphoinositide product of one enzyme may subsequently serve as a substrate for another to generate a different phosphoinositide species. This regulatory mechanism not only enables the transient generation of phosphoinositides on membranes, but also more complex sequential or bidirectional conversion pathways, and phosphoinositides can also be transferred between organelles via membrane contacts. It is this capacity to fine-tune phosphoinositide signals that makes them ideal regulators of membrane organization and dynamics, through their recruitment of signalling, membrane altering and lipid transfer proteins. Research spanning several decades has provided extensive evidence that phosphoinositides are major gatekeepers of membrane organization, with roles in endocytosis, exocytosis, autophagy, lysosome dynamics, vesicular transport and secretion, cilia, inter-organelle membrane contact, endosome maturation and nuclear function. By contrast, there has been remarkably little known about the role of phosphoinositides at mitochondria - an enigmatic and major knowledge gap, with challenges in reliably detecting phosphoinositides at this site. Here we review recent significant breakthroughs in understanding the role of phosphoinositides in regulating mitochondrial dynamics and metabolic function.
    Keywords:  Mitochondria; Mitochondrial fission; PI(4,5)P(2); PI3P; PI4P; Phosphoinositide
    DOI:  https://doi.org/10.1016/j.jbior.2023.101001
  3. J Leukoc Biol. 2023 Dec 06. pii: qiad155. [Epub ahead of print]
    The mitochondrial fission protein DRP1 influences memory CD8+ T cell formation and function.
    Marissa G Stevens, Frank M Mason, Timothy N J Bullock.
      Pharmacological methods for promoting mitochondrial elongation suggest that effector T cells can be altered to support a memory T cell-like metabolic state. Such mitochondrial elongation approaches may enhance the development of immunological memory. Therefore, we hypothesized that deletion of the mitochondrial fission protein, DRP1, would lead to mitochondrial elongation and generate a large memory T cell population, an approach that could be exploited to enhance vaccination protocols. We find that, as expected, while deletion of DRP1 from T cells in dLckCre x Drp1flfl does compromise the magnitude and functionality of primary effector CD8+ T cells, a disproportionately large pool of memory CD8+ T cells does form. In contrast to primary effector CD8+ T cells, DRP1-deficient memory dLckCre x Drp1flfl CD8+ T cells mount a secondary response comparable to control memory T cells with respect to kinetics, magnitude, and effector capabilities. Interestingly, the relative propensity to form memory cells in the absence of DRP1 was neither associated with differentiation toward more memory precursor CD8+ T cells nor decreased cellular death of effector T cells. Instead, the tendency to form memory CD8+ T cells in the absence of DRP1 is associated with decreased TCR expression. Remarkably, in a competitive environment with DRP1-replete CD8+ T cells, the absence of DRP1 from CD8+ T cells compromised the generation of primary, memory and secondary responses, indicating that approaches targeting DRP1 need to be carefully tailored.
    Keywords:  CD8+ T cell; Cell Death; Cytokine; Differentiation; Memory T cell; Metabolism; Mitochondria; T cell receptor
    DOI:  https://doi.org/10.1093/jleuko/qiad155
  4. Front Physiol. 2023 ;14 1284410
    Mitochondrial dynamics and metabolism across skin cells: implications for skin homeostasis and aging.
    Ines Martic, Federica Papaccio, Barbara Bellei, Maria Cavinato.
      Aging of human skin is a complex process leading to a decline in homeostasis and regenerative potential of this tissue. Mitochondria are important cell organelles that have a crucial role in several cellular mechanisms such as energy production and free radical maintenance. However, mitochondrial metabolism as well as processes of mitochondrial dynamics, biogenesis, and degradation varies considerably among the different types of cells that populate the skin. Disturbed mitochondrial function is known to promote aging and inflammation of the skin, leading to impairment of physiological skin function and the onset of skin pathologies. In this review, we discuss the essential role of mitochondria in different skin cell types and how impairment of mitochondrial morphology, physiology, and metabolism in each of these cellular compartments of the skin contributes to the process of skin aging.
    Keywords:  aging; mitochondria; skin; skin cells; skin homeostasis
    DOI:  https://doi.org/10.3389/fphys.2023.1284410
  5. Semin Cell Dev Biol. 2024 Mar 15. pii: S1084-9521(23)00169-6. [Epub ahead of print]156 253-265
    Collective mitochondrial dynamics resolve conflicting cellular tensions: From plants to general principles.
    Joanna M Chustecki, Iain G Johnston.
      Mitochondria play diverse and essential roles in eukaryotic cells, and plants are no exception. Plant mitochondria have several differences from their metazoan and fungal cousins: they often exist in a fragmented state, move rapidly on actin rather than microtubules, have many plant-specific metabolic features and roles, and usually contain only a subset of the complete mtDNA genome, which itself undergoes frequent recombination. This arrangement means that exchange and complementation is essential for plant mitochondria, and recent work has begun to reveal how their collective dynamics and resultant "social networks" of encounters support this exchange, connecting plant mitochondria in time rather than in space. This review will argue that this social network perspective can be extended to a "societal network", where mitochondrial dynamics are an essential part of the interacting cellular society of organelles and biomolecules. Evidence is emerging that mitochondrial dynamics allow optimal resolutions to competing cellular priorities; we will survey this evidence and review potential future research directions, highlighting that plant mitochondria can help reveal and test principles that apply across other kingdoms of life. In parallel with this fundamental cell biology, we also highlight the translational "One Health" importance of plant mitochondrial behaviour - which is exploited in the production of a vast amount of crops consumed worldwide - and the potential for multi-objective optimisation to understand and rationally re-engineer the evolved resolutions to these tensions.
    Keywords:  MtDNA inheritance; MtDNA maintenance; Multi-objective optimisation; Plant mitochondrial dynamics; Social network
    DOI:  https://doi.org/10.1016/j.semcdb.2023.09.005
  6. Front Cell Dev Biol. 2023 ;11 1307502
    Dynamics of mitochondrial membranes under photo-oxidative stress with high spatiotemporal resolution.
    Vincent Loriette, Alexandra Fragola, Sergei G Kruglik, Susmita Sridhar, Antoine Hubert, François Orieux, Eduardo Sepulveda, Franck Sureau, Stephanie Bonneau.
      In our study, we harnessed an original Enhanced Speed Structured Illumination Microscopy (Fast-SIM) imaging setup to explore the dynamics of mitochondrial and inner membrane ultrastructure under specific photo-oxidation stress induced by Chlorin-e6 and light irradiation. Notably, our Fast-SIM system allowed us to observe and quantify a distinct remodeling and shortening of the mitochondrial structure after 60-80 s of irradiation. These changes were accompanied by fusion events of adjacent inner membrane cristae and global swelling of the organelle. Preceding these alterations, a larger sequence was characterized by heightened dynamics within the mitochondrial network, featuring events such as mitochondrial fission, rapid formation of tubular prolongations, and fluctuations in cristae structure. Our findings provide compelling evidence that, among enhanced-resolution microscopy techniques, Fast-SIM emerges as the most suitable approach for non-invasive dynamic studies of mitochondrial structure in living cells. For the first time, this approach allows quantitative and qualitative characterization of successive steps in the photo-induced oxidation process with sufficient spatial and temporal resolution.
    Keywords:  Chlorin-e6; dynamics; live cell imaging; mitochondria; oxidation; shape changes; structured illumination microscopy (SIM); sub-organelles structures
    DOI:  https://doi.org/10.3389/fcell.2023.1307502
  7. Cell Rep. 2023 Dec 01. pii: S2211-1247(23)01540-1. [Epub ahead of print]42(12): 113528
    Apolipoproteins L1 and L3 control mitochondrial membrane dynamics.
    Laurence Lecordier, Paul Heo, Jonas H Graversen, Dorle Hennig, Maria Kløjgaard Skytthe, Alexandre Cornet d'Elzius, Frédéric Pincet, David Pérez-Morga, Etienne Pays.
      Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1, controls PI4KB activity through interaction with PI4KB and neuronal calcium sensor-1 or calneuron-1. Both APOLs are present in Golgi-derived autophagy-related protein 9A vesicles, which are involved in PI4KB trafficking. Like APOL3-KO, APOL1Δ induces PI4KB dissociation from APOL3, linked to reduction of mitophagy flux and production of mitochondrial reactive oxygen species. APOL1 and APOL3, respectively, can interact with the mitophagy receptor prohibitin-2 and the mitophagosome membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). While APOL1 conditions PI4KB and APOL3 involvement in mitochondrion fission and mitophagy, APOL3-VAMP8 interaction promotes fusion between mitophagosomal and endolysosomal membranes. We propose that APOL3 controls mitochondrial membrane dynamics through interactions with the fission factor PI4KB and the fusion factor VAMP8.
    Keywords:  APOL1 risk variants; COVAN; COVID-19-associated nephropathy; CP: Cell biology; HIV-associated nephropathy; HIVAN; inflammation; interferon 1; kidney disease; mitochondrion fission/fusion; mitophagy
    DOI:  https://doi.org/10.1016/j.celrep.2023.113528
  8. Neural Regen Res. 2024 Jul 01. 19(7): 1407-1408
    Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis.
    Naomi Hartopp, Andrea Markovinovic, Christopher Cj Miller, Patricia Gomez-Suaga.
      
    DOI:  https://doi.org/10.4103/1673-5374.387988
  9. Biol Trace Elem Res. 2023 Dec 07.
    The Footprints of Mitochondrial Fission and Apoptosis in Fluoride-Induced Renal Dysfunction.
    Qiyong Zuo, Lin Lin, Yuling Zhang, Mohammad Mehdi Ommati, Hongwei Wang, Jing Zhao.
      Fluoride (F) is widely distributed in the environment and poses serious health risks to humans and animals. Although a good body of literature demonstrates a close relationship between F content and renal system performance, there is no satisfactory information on the involved intracellular routes. Hence, this study used histopathology and mitochondrial fission to explore fluorine-induced nephrotoxicity further. For this purpose, mice were exposed to the F ion (0, 25, 50, 100 mg/L) for 90 days. The effects of different F levels on renal pathomorphology and ion metabolism were assessed using hematoxylin and eosin (H&E), periodic acid-Schiff stain (PAS), periodic acid-silver methenamine (PASM), Prussian blue (PB), and alkaline phosphatase (ALP) staining. The results showed that F could lead to glomerular atrophy, tubular degeneration, and vacuolization. Meanwhile, F also could increase glomerular and tubular glycoproteins; made thickening of the renal capsule membrane and thickening of the tubular basement membrane; led to the accumulation of iron ions in the tubules; and increased in glomerular alp and decreased tubular alp. Concomitantly, IHC results showed that F significantly upregulated the expression levels of mitochondrial fission-related proteins, including mitochondrial fission factor (Mff), fission 1 (Fis1), and mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), ultimately caused apoptosis. To sum up, excessive fluorine has a strong nephrotoxicity effect, disrupting the balance of mitochondrial fission and fusion, interfering with the process of mitochondrial fission, and then causing damage to renal tissue structure and apoptosis.
    Keywords:  Apoptosis; Fluorosis; Mitochondrion; Nephrotoxicity
    DOI:  https://doi.org/10.1007/s12011-023-03994-5
  10. Biol Lett. 2023 Dec;19(12): 20230375
    Mitonuclear interactions modulate nutritional preference.
    M Florencia Camus, Sahutchai Inwongwan.
      In nature, organisms are faced with constant nutritional options which fuel key life-history traits. Studies have shown that species can actively make nutritional decisions based on internal and external cues. Metabolism itself is underpinned by complex genomic interactions involving components from both nuclear and mitochondrial genomes. Products from these two genomes must coordinate how nutrients are extracted, used and recycled. Given the complicated nature of metabolism, it is not well understood how nutritional choices are affected by mitonuclear interactions. This is under the rationale that changes in genomic interactions will affect metabolic flux and change physiological requirements. To this end we used a large Drosophila mitonuclear genetic panel, comprising nine isogenic nuclear genomes coupled to nine mitochondrial haplotypes, giving a total of 81 different mitonuclear genotypes. We use a capillary-based feeding assay to screen this panel for dietary preference between carbohydrate and protein. We find significant mitonuclear interactions modulating nutritional choices, with these epistatic interactions also being dependent on sex. Our findings support the notion that complex genomic interactions can place a constraint on metabolic flux. This work gives us deeper insights into how key metabolic interactions can have broad implications on behaviour.
    Keywords:  behaviour; mitonuclear epistasis; mtDNA; nutrition
    DOI:  https://doi.org/10.1098/rsbl.2023.0375
  11. Inflammation. 2023 Dec 06.
    Upregulation of UHRF1 Promotes PINK1-mediated Mitophagy to Alleviates Ferroptosis in Diabetic Nephropathy.
    Hongfei Ji, Yanyan Zhao, Xiaojun Ma, Lina Wu, Feng Guo, Fengjuan Huang, Yi Song, Jiao Wang, Guijun Qin.
      Diabetic nephropathy (DN) is a common diabetic complication. Studies show that mitophagy inhibition induced-ferroptosis plays a crucial role in DN progression. UHRF1 is associated with mitophagy and is highly expression in DN patients, however, the effect of UHRF1 on DN is still unclear. Thus, in this study, we aimed to investigate whether UHRF1 involves DN development by the mitophagy/ferroptosis pathway. We overexpressed UHRF1 using an adeno-associated virus 9 (AAV9) system in high-fat diet/streptozotocin-induced diabetic mice. Renal function index, pathological changes, mitophagy factors, and ferroptosis factors were detected in vivo. High-glucose cultured human renal proximal tubular (HK-2) cells were used as in vitro models to investigate the mechanism of UHRF1 in DN. We found that diabetic mice exhibited kidney damage, which was alleviated by UHRF1 overexpression. UHRF1 overexpression promoted PINK1-mediated mitophagy and inhibited the expression of thioredoxin interacting protein (TXNIP), a factor associated with mitochondrial dysfunction. Additionally, UHRF1 overexpression alleviated lipid peroxidation and free iron accumulation, and upregulated the expression of GPX4 and Slc7a11, indicating the inhibition effect of UHRF1 overexpression on ferroptosis. We further investigated the mechanism of UHRF1 in the mitophagy/ferroptosis pathway in DN. We found that UHRF1 overexpression promoted PINK1-mediated mitophagy via inhibiting TXNIP expression, thus suppressing ferroptosis. These findings confirmed that upregulation of UHRF1 expression alleviates DN, indicating that UHRF1 has a reno-protective effect against DN.
    Keywords:  UHRF1; diabetic nephropathy; ferroptosis; mitophagy
    DOI:  https://doi.org/10.1007/s10753-023-01940-0
  12. PeerJ. 2023 ;11 e16497
    Role of Pink1-mediated mitophagy in adenomyosis.
    Minmin Chen, Wei Wang, Xianyun Fu, Yongli Yi, Kun Wang, Meiling Wang.
      Abstract Background: Recent studies indicate that endometrial hypoxia plays a critical role in adenomyosis (AM) development. Mitochondria are extremely sensitive to hypoxic damage, which can result in both morphological and functional impairment. Mitophagy is a crucial mechanism for preserving mitochondrial quality by selectively removing damaged mitochondria, thus ensuring the proper functioning of the entire mitochondrial network. In response to hypoxia, PINK1 is activated as a regulator of mitophagy, but its role in AM requires further study.Objective: To explore the potential mechanism of mitophagy mediated by PINK1 in the pathogenesis of AM.
    Method: The study compared PINK1, Parkin, OPTIN, P62, and NDP52 protein expression levels in patients with or without AM using clinical specimens and an AM mouse model. Pathological changes were compared using HE staining. Immunofluorescence and western blot were used to detect protein expression levels. Endometrial stromal cells (ESC) were isolated and examined for mitophagy, protein expression level, and cell invasion ability.
    Results: Both the endometrial tissue from patients with AM and AM ESC displayed an upregulation of protein levels for PINK1, Parkin, OPTIN, P62, and NDP52 when compared with the control group. Then, HE staining confirmed the successful establishment of the AM mouse model. Moreover, the ultrastructural analysis using transmission electron microscopy revealed that AM mice's endometrial glandular epithelial and stromal cells had exhibited swollen, deformed, and reduced mitochondria along with an increase in the number of lysosomes and mitochondrial autophagosomes. The protein levels of PINK1, Parkin, OPTIN, P62, and NDP52 in uterine tissue from AM mice were noticeably increased, accompanied by a considerable upregulation of ROS levels compared to the control group. In addition, cells in the AM group showed remarkably elevated mitophagy and invasion potentials compared to the control group. In contrast, the cell invasion ability decreased following PINK1 knockdown using the RNA interference technique.
    Conclusion: The high levels of PINK1-mediated mitophagy have been found in AM. The upregulation in mitophagy contributes to mitochondrial damage, which may result in the abnormal invasion characteristic of AM.
    Keywords:  Adenomyosis; Mitophagy; PINK1
    DOI:  https://doi.org/10.7717/peerj.16497
  13. Comput Struct Biotechnol J. 2023 ;21 5609-5619
    Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity.
    Sophie Charrasse, Titouan Poquillon, Charlotte Saint-Omer, Manuela Pastore, Benoit Bordignon, Richard E Frye, Christelle Reynes, Victor Racine, Abdel Aouacheria.
      Mitochondria are essential organelles that play crucial roles in cellular energy metabolism, calcium signaling and apoptosis. Their importance in tissue homeostasis and stress responses, combined to their ability to transition between various structural and functional states, make them excellent organelles for monitoring cellular health. Quantitative assessment of mitochondrial morphology can therefore provide valuable insights into environmentally-induced cell damage. High-content screening (HCS) provides a powerful tool for analyzing organelles and cellular substructures. We developed a fully automated and miniaturized HCS wet-plus-dry pipeline (MITOMATICS) exploiting mitochondrial morphology as a marker for monitoring cellular health or damage. MITOMATICS uses an in-house, proprietary software (MitoRadar) to enable fast, exhaustive and cost-effective analysis of mitochondrial morphology and its inherent diversity in live cells. We applied our pipeline and big data analytics software to assess the mitotoxicity of selected chemicals, using the mitochondrial uncoupler CCCP as an internal control. Six different pesticides (inhibiting complexes I, II and III of the mitochondrial respiratory chain) were tested as individual compounds and five other pesticides present locally in Occitanie (Southern France) were assessed in combination to determine acute mitotoxicity. Our results show that the assayed pesticides exhibit specific signatures when used as single compounds or chemical mixtures and that they function synergistically to impact mitochondrial architecture. Study of environment-induced mitochondrial damage has the potential to open new fields in mechanistic toxicology, currently underexplored by regulatory toxicology and exposome research. Such exploration could inform health policy guidelines and foster pharmacological intervention, water, air and soil pollution control and food safety.
    Keywords:  Cellular stress; Confocal microscopy; Environmental health; High content analysis; Live-cell imaging; Mitochondria; Pesticides; Quantitative imaging
    DOI:  https://doi.org/10.1016/j.csbj.2023.11.015
  14. Am J Physiol Cell Physiol. 2023 Dec 04.
    RTA 408 ameliorates diabetic cardiomyopathy by activating Nrf2 to regulate mitochondrial fission and fusion and inhibiting NF-κB-mediated inflammation.
    Jinjin Hao, Jiedong Zhou, Songqing Hu, Peipei Zhang, Haowei Wu, Juntao Yang, Bingjie Zhao, Hanxuan Liu, Hui Lin, Jufang Chi, Dajun Lou.
      Diabetic cardiomyopathy (dCM) is a major complication of diabetes; however, specific treatments for dCM are currently lacking. RTA 408, a semisynthetic triterpenoid, has shown therapeutic potential against various diseases by activating the Nrf2 (Nuclear factor erythroid 2-related factor 2) signaling pathway. We established in vitro and in vivo models using high-glucose toxicity and db/db mice, respectively, to simulate dCM. Our results demonstrated that RTA 408 activated Nrf2 and alleviated various dCM-related cardiac dysfunctions, both in vivo and in vitro. Additionally, it was found that silencing the Nrf2 gene eliminated the cardioprotective effect of RTA 408. RTA 408 ameliorated oxidative stress in dCM mice and HG-exposed H9C2 cells by activating Nrf2, inhibiting mitochondrial fission, exerting anti-inflammatory effects through the Nrf2/NF-κB axis, and ultimately suppressing apoptosis, thereby providing cardiac protection against dCM. These findings provide valuable insights for potential dCM treatments.
    Keywords:  Diabetic cardiomyopathy; Mitochondrial fission and fusion; Nrf2; Oxidative stress; RTA 408
    DOI:  https://doi.org/10.1152/ajpcell.00467.2023
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