Journal of Biomedical Science

, Volume 9, Issue 6, pp 475–487

How mitochondrial damage affects cell function

  • Andrew M. James
  • Michael P. Murphy

DOI: 10.1007/BF02254975

Cite this article as:
James, A.M. & Murphy, M.P. J Biomed Sci (2002) 9: 475. doi:10.1007/BF02254975


The pathophysiology of mitochondrial DNA (mtDNA) diseases is caused by increased cell death and dysfunction due to the accumulation of mutations to mtDNA. While the disruption of oxidative phosphorylation is central to mtDNA diseases, many other factors, such as Ca2+ dyshomeostasis, increased oxidative stress and defective turnover of mitochondrial proteins, may also contribute. The relative importance of these processes in causing cell dysfunction and death is uncertain. It is also unclear whether these damaging processes lead to the disease phenotype through affecting cell function, increasing cell death or a combination of both. These uncertainties limit our understanding of mtDNA disease pathophysiology and our ability to develop rational therapies. Here, we outline how the accumulation of mtDNA mutations can lead to cell dysfunction by altering oxidative phosphorylation, Ca2+ homeostasis, oxidative stress and protein turnover and discuss how these processes affect cell function and susceptibility to cell death. A better understanding of these processes will eventually clarify why particular mtDNA mutations cause defined syndromes in some cases but not in others and why the same mutation can lead to different phenotypes.

Key Words

Mitochondria Mitochondrial DNA Apoptosis Autophagy Reactive oxygen species Permeability transition pore Calcium ATP Membrane potential 

Copyright information

© National Science Council 2002

Authors and Affiliations

  • Andrew M. James
    • 1
  • Michael P. Murphy
    • 1
  1. 1.MRC-Dunn Human Nutrition UnitCambridgeUK