Mitochondrial complex I subunit deficiency promotes pancreatic α-cell proliferation

Yu, Xuefei; Arden, Catherine; Berlinguer‐Palmini, Rolando; Chen, Chun; Bradshaw, Carla; Whitehall, Julia C; White, Margaret A.; Anderson, Scott J.; Kattner, Nicole; Shaw, James; Turnbull, Doug; Greaves, Laura C.; Walker, Mark S.

doi:10.1016/j.molmet.2022.101489

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…The reason for increased α-cell number is unclear. Interestingly, in mouse models of mitochondria dysfunction, where complex I expression was decreased, pancreatic α-cell mass was also increased (64). Whether increase in α-cells is due to neogenesis or transdifferentiating cells is also unknown, but we did not observe any significant differences in markers for proliferation or cell death.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Carlein,

Hoffmann,

Amaral

et al. 2024

Preprint

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Barth syndrome is a multisystem genetic disorder caused by mutation inTAFAZZIN, a gene that encodes a phospholipid:lysophospholipid transacylase important for cardiolipin remodeling. Barth Syndrome patients suffer from a number of symptoms including early heart failure, fatigue, and systemic metabolic alterations, including hypoglycemia. The endocrine pancreas is central to glucose homeostasis, however, the impact of defective cardiolipin remodeling on pancreatic islet function and the consequences for systemic metabolism is unclear. Surprisingly, in a mouse model with globalTAFAZZINknockdown, we observed improved glucose tolerance compared to wildtype littermates. We show that pancreatic islet metabolism and secretory function are robustly maintained through various compensatory mechanisms including increased glucose uptake and increased mitochondrial volume. Transcriptomics analyses revealed increased expression of genes encoding proteins involved in N-acetylglucosamine synthesis and proteinO-linked N-acetylglucosaminylation. These pathways might provide a molecular mechanism for coupling metabolic changes to mitochondrial volume regulation.

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Section: Discussionmentioning

confidence: 99%

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Carlein,

Hoffmann,

Amaral

et al. 2024

Preprint

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“…Importantly, the identification of the proteins with western blot and immunofluorescence have been previously correlated to its genetic loss determined by activity assays and by spectrophotometer [42,49,50]. In this way, mitochondrial dysfunction has been investigated in both primary and secondary mitochondrial diseases, gathering information at a single cell level in muscle [47,51], neurons and brain [52][53][54][55], pancreas [56] and bone [57].…”

Section: Discussionmentioning

confidence: 99%

Resistance Exercise Training Rescues Mitochondrial Dysfunction in Skeletal Muscle of Patients with Myotonic Dystrophy Type 1

Di Leo,

Lawless,

Roussel

et al. 2023

Journal of Neuromuscular Diseases

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Background: Myotonic dystrophy type 1 (DM1) is a dominant autosomal neuromuscular disorder caused by the inheritance of a CTG triplet repeat expansion in the Dystrophia Myotonica Protein Kinase (DMPK) gene. At present, no cure currently exists for DM1 disease. Objective: This study investigates the effects of 12-week resistance exercise training on mitochondrial oxidative phosphorylation in skeletal muscle in a cohort of DM1 patients (n = 11, men) in comparison to control muscle with normal oxidative phosphorylation. Methods: Immunofluorescence was used to assess protein levels of key respiratory chain subunits of complex I (CI) and complex IV (CIV), and markers of mitochondrial mass and cell membrane in individual myofibres sampled from muscle biopsies. Using control’s skeletal muscle fibers population, we classified each patient’s fibers as having normal, low or high levels of CI and CIV and compared the proportions of fibers before and after exercise training. The significance of changes observed between pre- and post-exercise within patients was estimated using a permutation test. Results: At baseline, DM1 patients present with significantly decreased mitochondrial mass, and isolated or combined CI and CIV deficiency. After resistance exercise training, in most patients a significant increase in mitochondrial mass was observed, and all patients showed a significant increase in CI and/or CIV protein levels. Moreover, improvements in mitochondrial mass were correlated with the one-repetition maximum strength evaluation. Conclusions: Remarkably, 12-week resistance exercise training is sufficient to partially rescue mitochondrial dysfunction in DM1 patients, suggesting that the response to exercise is in part be due to changes in mitochondria.

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“…It receives electrons from nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH) and transfers them to ubiquinone. The energy obtained is used to pump protons from the matrix side of the inner mitochondrial membrane to the cytoplasmic side, which is important for the oxidative phosphorylation process [ [1] , [2] , [3] ]. Complex I consists of 45 subunits encoded by nuclear DNA and mitochondrial DNA (mtDNA), of which 7 subunits encoded by mtDNA (ND1–ND6 and ND4L) are located on the membrane arm of complex I, and are related to the ubiquinone reduction and proton translocation mechanisms [ [4] , [5] , [6] ].…”

Section: Mt-nd1 Gene Expression and Biological Functionmentioning

confidence: 99%

Mitochondrial complex I subunit MT-ND1 mutations affect disease progression

Lin,

Zhou,

Xue

2024

Heliyon

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Mitochondrial complex I subunit deficiency promotes pancreatic α-cell proliferation

Cited by 5 publications

References 32 publications

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome

Resistance Exercise Training Rescues Mitochondrial Dysfunction in Skeletal Muscle of Patients with Myotonic Dystrophy Type 1

Mitochondrial complex I subunit MT-ND1 mutations affect disease progression

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