Communications Biology (Jan 2023)
OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases
- Gabriel Sturm,
- Kalpita R. Karan,
- Anna S. Monzel,
- Balaji Santhanam,
- Tanja Taivassalo,
- Céline Bris,
- Sarah A. Ware,
- Marissa Cross,
- Atif Towheed,
- Albert Higgins-Chen,
- Meagan J. McManus,
- Andres Cardenas,
- Jue Lin,
- Elissa S. Epel,
- Shamima Rahman,
- John Vissing,
- Bruno Grassi,
- Morgan Levine,
- Steve Horvath,
- Ronald G. Haller,
- Guy Lenaers,
- Douglas C. Wallace,
- Marie-Pierre St-Onge,
- Saeed Tavazoie,
- Vincent Procaccio,
- Brett A. Kaufman,
- Erin L. Seifert,
- Michio Hirano,
- Martin Picard
Affiliations
- Gabriel Sturm
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
- Kalpita R. Karan
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
- Anna S. Monzel
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
- Balaji Santhanam
- Departments of Biological Sciences, Systems Biology, and Biochemistry and Molecular Biophysics, Institute for Cancer Dynamics, Columbia University
- Tanja Taivassalo
- Department of Physiology and Functional Genomics, Clinical and Translational Research Building, University of Florida
- Céline Bris
- Department of Genetics and Neurology, Angers Hospital
- Sarah A. Ware
- Department of Medicine, Vascular Medicine Institute and Center for Metabolic and Mitochondrial Medicine, University of Pittsburgh
- Marissa Cross
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
- Atif Towheed
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
- Albert Higgins-Chen
- Department of Psychiatry, Yale University School of Medicine
- Meagan J. McManus
- Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia
- Andres Cardenas
- Department of Epidemiology and Population Health, Stanford University
- Jue Lin
- Department of Biochemistry and Biophysics, University of California
- Elissa S. Epel
- Department of Psychiatry and Behavioral Sciences, University of California
- Shamima Rahman
- Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, and Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust
- John Vissing
- Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen
- Bruno Grassi
- Department of Medicine, University of Udine
- Morgan Levine
- Altos Labs
- Steve Horvath
- Altos Labs
- Ronald G. Haller
- Neuromuscular Center, Institute for Exercise and Environmental Medicine of Texas Health Resources and Department of Neurology, University of Texas Southwestern Medical Center
- Guy Lenaers
- Department of Genetics and Neurology, Angers Hospital
- Douglas C. Wallace
- Center for Mitochondrial and Epigenomic Medicine, The Children’s Hospital of Philadelphia
- Marie-Pierre St-Onge
- Center of Excellence for Sleep & Circadian Research and Division of General Medicine, Department of Medicine, Columbia University Irving Medical Center
- Saeed Tavazoie
- Departments of Biological Sciences, Systems Biology, and Biochemistry and Molecular Biophysics, Institute for Cancer Dynamics, Columbia University
- Vincent Procaccio
- Department of Genetics and Neurology, Angers Hospital
- Brett A. Kaufman
- Department of Medicine, Vascular Medicine Institute and Center for Metabolic and Mitochondrial Medicine, University of Pittsburgh
- Erin L. Seifert
- Department of Pathology and Genomic Medicine, and MitoCare Center, Thomas Jefferson University
- Michio Hirano
- Department of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center
- Martin Picard
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
- DOI
- https://doi.org/10.1038/s42003-022-04303-x
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 1 – 22
Abstract
A meta-analysis of 17 cohorts of mitochondrial disease patients reveals that OxPhos defects are associated with signs of hypermetabolism. Experiments in patient-derived fibroblast show that mitochondrial OxPhos defects trigger hypermetabolism in a cell-autonomous manner and this is linked to accelerated telomere shortening and epigenetic aging.
