Short telomeres in mitochondrial DNA depletion disorders

Yumi Dille; Emmanouil Rampakakis; Geraldine Aubert; Christelle Dassi; William Mannherz; Saoussen Berrahmoune; Myriam Srour; Daniela Buhas; Suneet Agarwal; Kenneth A Myers

doi:10.1016/j.mito.2026.102131

Short telomeres in mitochondrial DNA depletion disorders

Mitochondrion. 2026 May:88:102131. doi: 10.1016/j.mito.2026.102131. Epub 2026 Feb 10.

Authors

Affiliations

¹ Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, Quebec, Canada.
² Medical Affairs, JSS Medical Research, Montreal, Québec, Canada; Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.
³ Repeat Diagnostics Inc., North Vancouver, British Columbia, Canada; Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, British Columbia, Canada.
⁴ Child Health & Human Development Program, Research Institute of the McGill University Health Centre, 2155 Guy Street, Suite 500, Montreal, Quebec, Canada.
⁵ Harvard/MIT MD-PhD Program, Harvard Medical School, Boston, MA, USA.
⁶ Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, Quebec, Canada; Child Health & Human Development Program, Research Institute of the McGill University Health Centre, 2155 Guy Street, Suite 500, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, Quebec, Canada.
⁷ Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
⁸ Division of Hematology/Oncology and Stem Cell Program, Boston Children's Hospital, Pediatric Oncology, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: suneet.agarwal@childrens.harvard.edu.
⁹ Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, Quebec, Canada; Child Health & Human Development Program, Research Institute of the McGill University Health Centre, 2155 Guy Street, Suite 500, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, Quebec, Canada. Electronic address: kenneth.myers@mcgill.ca.

PMID: 41679577
DOI: 10.1016/j.mito.2026.102131

Abstract

Mitochondrial DNA (mtDNA) depletion disorders (MDDs) are rare, genetically diverse conditions marked by a significant reduction in mtDNA, primarily affecting energy-demanding tissues such as muscle, liver, and brain, sometimes leading to catastrophic multisystem failure. In a cohort of patients with MDDs, we measured telomere length in lymphocytes, granulocytes, T cells, and B cells, and compared to healthy controls. Telomere length was shorter overall in patients with MDDs, with the most significant differences observed in granulocytes. The observation that mtDNA depletion is associated with shorter telomeres may provide insight into MDD pathophysiology. Telomere length may have potential as a biomarker in mitochondrial disease, but further study is needed.

Keywords: C10orf2; DGUOK; Mitochondrial DNA depletion disorders; POLG; RRM2B; SUCLA2; SUCLG1; TK2; TYMP; Telomere length; Telomeres.

MeSH terms

DNA, Mitochondrial* / genetics
Female
Humans
Male
Mitochondrial Diseases* / genetics
Mitochondrial Diseases* / pathology
Telomere Shortening*
Telomere*

Substances

DNA, Mitochondrial