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Mitochondrial complex I subunit deficiency promotes pancreatic α-cell proliferation

Lookup NU author(s): Xuefei Yu, Dr Catherine ArdenORCiD, Dr Rolando Berlinguer PalminiORCiD, Dr Chun ChenORCiD, Carla Bradshaw, Anna Smith, Dr Julia Whitehall, Dr Michael White, Dr Scott Anderson, Dr Nicole Kattner, Professor James Shaw, Emeritus Professor Doug Turnbull, Dr Laura Greaves, Professor Mark Walker



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 The AuthorsObjective: There is strong evidence that mitochondrial DNA mutations and mitochondrial dysfunction play a role in diabetes pathogenesis. The homozygous knock-in mtDNA mutator mouse is a model of premature aging due to the accumulation of mitochondrial DNA mutations. We used this mouse model to investigate the relationship between mitochondrial subunit expression and pancreatic islet cell composition. Methods: Quadruple immunofluorescence was used to quantify mitochondrial subunit expression (complex I and IV) and cell composition in pancreatic islets from mitochondrial DNA mutator mice (PolgAmut/mut) and control C57BL/6 mice at 12 and 44 weeks of age. Results: Mitochondrial complex I subunit expression was decreased in islets from 12 week PolgAmut/mut mice. This complex I deficiency persisted with age and was associated with decreased insulin staining intensity at 44 weeks. Complex I deficiency was greater in α-cells compared with β-cells in islets from 44 week PolgAmut/mut mice. Islet cell composition was normal in 12 week PolgAmut/mut mice, but the β: α cell ratio was decreased in islets from 44 week PolgAmut/mut mice. This was due to an increase in α-cell number linked to an increase in α-cell proliferation. Conclusion: Complex I deficiency promotes α-cell proliferation and alters islet cell composition.

Publication metadata

Author(s): Yu X, Arden C, Berlinguer-Palmini R, Chen C, Bradshaw C, Smith AL, Whitehall J, White M, Anderson S, Kattner N, Shaw J, Turnbull D, Greaves LC, Walker M

Publication type: Article

Publication status: Published

Journal: Molecular Metabolism

Year: 2022

Volume: 60

Print publication date: 01/06/2022

Online publication date: 04/04/2022

Acceptance date: 28/03/2022

Date deposited: 03/07/2023

ISSN (electronic): 2212-8778

Publisher: Elsevier GmbH


DOI: 10.1016/j.molmet.2022.101489

PubMed id: 35390502


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Funder referenceFunder name
203105/Z/16/ZWellcome Trust
MR/L016354/1Medical Research Council (MRC)
Wellcome Trust