Mitochondrial Genetics in Cancer

Group Leader:
Prof Laura Greaves

Our work centres on understanding the downstream consequences of mitochondrial DNA (mtDNA) mutations in CRC, particularly how these mutations lead to functional changes in oxidative phosphorylation (OXPHOS), and the resulting impact on tumour biology. Mitochondria are essential for ATP production and support a wide range of biosynthetic and signalling processes required for cell growth, differentiation, and survival. We have demonstrated that pathogenic mtDNA mutations, which accumulate with age, are present in approximately 60% of colorectal adenocarcinomas.

They frequently result in defects in OXPHOS, particularly affecting complexes I and IV (Smith et al, Nature Cancer 2020). Our data indicate that they are under positive selection during tumour development and play a significant role in shaping tumour behaviour through metabolic reprogramming.

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Lab Reports

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Recent Publications

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Lab Members

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Recent Publications

*corresponding author

2026

MacVicar T, Greaves LC, Gammage PA, Tait SWG, Fisher-Wellman KH, Freedman G. Cancer as a window into mitochondrial biology. Cell Metab. 2026(6):1085-1088.

2025

Mullins A, Yu X, Smith ALM, Merces G, Shaw JAM, Greaves LC, Walker M, Arden C. Single-cell analysis of oxidative phosphorylation protein expression in pancreatic islets in type 2 diabetes. J Endocrinol. 2025;267(1).

Low SSP, Greaves L, Silk R, Semple CA, Gourley C. Spectrum and Impact of Mitochondrial DNA Mutations in Ovarian Cancer. Int J Mol Sci. 2025(22).

2024

Kelly G, Kataura Y, Ma G, Panek J, Salmonowicz H, Davis A, Kendall H, Brookes C, Moscoh D, Tora A, Banks P, Nelson G, Dobby L, Pitrez P, Booth L, Costello L, Richardson GD, Lovat P, Przyborski S, Lino Ferreira, Greaves L, Szczepanowska K, von Zglinicki T, Miwa S, Brown M, Flagle M, Oblong JE, Bascom CC, Carroll B, Reynisson J, Korolchuk VI. Suppressed basal mitophagy drives cellular ageing phenotypes, Dev Cell. 2024; 2024 Aug 5;59(15):1924-1939.e7

2023

Victorelli S, Salmonowicz, H, Chapman J, Martini H, Vizioli MG, Riley JS, Cloix C, Hall-Younger E, Espindola-Netto JM, Jurk D, Lagnado AB, Gomez LS, Farr JN, Saul D, Reed R, Kelly G, Eppard M, Greaves LC, Dou Z, Pirius N, Szczepanowska S, Porritt RA, Huang H, Huang TY, Mann DA, Masuda CA, Khosla S, Dai H, Kaufmann SJ, Zacharioudakis E, Gavathiotis E, LeBrasseur N, Lei X, Sainz AG, Korolchuk VI, Adams PD, Shadel GS, Tait SWG, Passos JF. Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature. 2023;622(7983):627-636

Pickett SJ, Hudson G, Greaves LC*. Single-cell multiomic analyses sheds light on mitochondrial mutational selection. Nat Genet. 2023;55(7):1083-1085

2022

Sachdeva A, Hart CA, Carey CD, Vincent AE, Greaves LC, Heer R, Oliveira P, Brown MD, Clarke NW, Turnbull DM. Automated quantitative high-throughput multiplex immunofluorescence pipeline to evaluate OXPHOS defects in formalin-fixed human prostate tissue. Sci Rep. 2022;12(1):6660.

Smith A, Whitehall JC, Greaves LC*. Mitochondrial DNA mutations in aging and cancer. Mol Oncol. 2022;16(18):3276-3294.

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. Mitochondrial complex I subunit deficiency promotes pancreatic α-cell proliferation. Mol Metab. 2022;60:101489.

2021

Fuller A, Okwose N, Scragg J, Eggett C, Luke P, Bandali A, Velicki R, Greaves L, MacGowan GA, Jakovljevic DG. The effect of age on mechanisms of exercise tolerance: Reduced arteriovenous oxygen difference causes lower oxygen consumption in older people. Exp Gerontol. 2021;149:111340.

Stamp C, Whitehall JC, Smith ALM, Houghton D, Bradshaw C, Stoll EA, Blain AP, Turnbull DM, Greaves LC*. Age-associated mitochondrial complex I deficiency is linked to increased stem cell proliferation rates in the mouse colon. Aging Cell. 2021;20(3):e13321.

2020

Smith ALM, Whitehall JC, Gay D, Bradshaw C, Robertson F, Blain AP, Houghton D, Hunt M, Sampson JN, Stamp C, Baker A, Russell OM, Johnson R, Richardson CA, Gupta B, McCallum I, Kelly S, Mathers JC, Heer R, Taylor RW, Perkins ND, Turnbull DM, Sansom OJ, Greaves LC*. Age-associated mitochondrial DNA mutations cause metabolic remodelling that contributes to accelerated intestinal tumorigenesis. Nat Cancer. 2020;1, 976–989

Dobson PF, Hipps D, Reeve AK, Laude A, Stamp C, Smith ALM, Deehan DJ, Turnbull DM, Greaves LC*. Mitochondrial dysfunction impairs in vitro osteogenesis, osteoclast function and accelerates age-related bone loss. Sci Rep. 2020;10(1):11643.

Lawless C, Greaves LC, Reeve AK, Turnbull DM, Vincent AE. The rise and rise of mitochondrial DNA mutations. Open Biol. 2020;10(5):200061.

Whitehall JC and Greaves LC*. Aberrant mitochondrial function in ageing and cancer. Biogerontology. 2020;21(4):445-459.

2019

Anderson R, Lagnado A, Maggiorani D, Walaszczyk A, Dookun E, Chapman J, Birch J, Salmonowicz H, Ogrodnik M, Jurk D, Proctor C, Correia-Melo C, Victorelli S, Fielder E, Berlinguer-Palmini R, Owens A, Greaves LC, Kolsky KL, Parini A, Douin-Echinard V, LeBrasseur NK, Arthur HM, Tual-Chalot S, Schafer MJ, Roos CM, Miller JD, Robertson N, Mann J, Adams PD, Tchkonia T, Kirkland JL, Mialet-Perez J, Richardson GD, Passos JF. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. 2019;38(5):e100492.

Breininger SP, Malcomson FC, Afshar S, Turnbull DM, Greaves L, Mathers JC. Effects of obesity and weight loss on mitochondrial structure and function and implications for colorectal cancer risk. Proc Nutr Soc. 2019;78(3):426-437.

Malcomson FC, Breininger SP, ElGendy K, Joel A, Ranathunga T, Hill T, Bradburn DM, Turnbull DM, Greaves LC, Mathers JC. Design and Baseline Characteristics of the BORICC Follow-Up (BFU) Study: a 12+ years follow-up of the Biomarkers Of Risk of Colorectal Cancer Study. Nutr Health. 2019;25(3):231-238.

Paish HL, Reed LH, Brown H, Bryan MC, Govaere O, Leslie J, Barksby BS, Garcia Macia M, Watson A, Xu X, Zaki MYW, Greaves L, Whitehall J, French J, White SA, Manas DM, Robinson SM, Spoletini G, Griffiths C, Mann DA, Borthwick LA, Drinnan MJ, Mann J, Oakley F. A novel bioreactor technology for modelling fibrosis in human and rodent precision-cut liver slices. Hepatology. 2019;70(4):1377-1391.

2018

Simard ML, Mourier A, Greaves LC, Taylor RW, Stewart JB. A novel histochemistry assay to assess and quantify focal cytochrome c oxidase deficiency. J Pathol. 2018;245(3):311-323.

Stamp C, Zupanic A, Sachdeva A, Stoll EA, Shanley DP, Mathers JC, Kirkwood TBL, Heer R, Simons BD, Turnbull DM, Greaves LC*. Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts. EBioMedicine. 2018;31:166-173.

Su T, Grady JP, Afshar S, McDonald SA, Taylor RW, Turnbull DM, Greaves LC*. Inherited pathogenic mitochondrial DNA mutations and gastrointestinal stem cell populations. J Pathol. 2018;246(4):427-432.

Su T, Turnbull DM, Greaves LC*. Roles of Mitochondrial DNA Mutations in Stem Cell Ageing. Genes (Basel). 2018;9(4).

Group Leader

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Laura Greaves

Lab Members

Senior scientific officer

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Zaniah Gonzalez

I am a Senior Scientific Officer with a background in stem cell biology, development, and the role of mitochondrial mutations in cancer. I completed my PhD in Regenerative Medicine at the University of Edinburgh and held several postdoctoral positions before joining the Greaves group -which operates as the sister lab to the Newcastle lab in Glasgow— to help steer our research forward. My role blends senior technical and operational leadership—keeping everything running smoothly, setting up reproducible protocols, and managing the day-to-day coordination across our Glasgow and Newcastle sites. I work with a high degree of independence to support both our immediate projects and long-term planning, which currently includes driving critical data collection for our MRC programme application and helping lay the groundwork for a future Centre of Research Excellence. I love using my varied technical background to help team members design and execute their experiments, ensuring our science is as impactful as possible.
Outside of the lab, I'm happiest spending quality time with my family, getting out into nature, cycling, or settling down with a great Sci-Fi book.

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