- 作者: Andrew M. James, Michael P. Murphy
- 作者服務機構: MRC-Dunn Human Nutrition Unit, Cambridge, UK
- 中文摘要: --
- 英文摘要: The pathophysiology of mitochondrial DNA (mtDNA)diseases is caused by increased cell death and dysfunc-tion due to the accumulation of mutations to mtDNA.While the disruption of oxidative phosphorylation is cen-tral to mtDNA diseases, many other factors, such as Cadyshomeostasis, increased oxidative stress and defec-tive turnover of mitochondrial proteins, may also con-tribute. The relative importance of these processes incausing cell dysfunction and death is uncertain. It is alsounclear whether these damaging processes lead to thedisease phenotype through affecting cell function, in-creasing cell death or a combination of both. Theseuncertainties limit our understanding of mtDNA diseasepathophysiology and our ability to develop rational ther-apies. Here, we outline how the accumulation of mtDNAmutations can lead to celldysfunction by altering oxida-tive phosphorylation, Ca homeostasis, oxidative stressand protein turnover and discuss how these processesaffect cell function and susceptibility to cell death. A bet-ter understanding of these processes will eventually clar-ify why particular mtDNA mutations cause defined syn-dromes in some cases but not in others and why thesame mutation can lead to different phenotypes.
- 中文關鍵字: --
- 英文關鍵字: Mitochondria, Mitochondrial DNA, Apoptosis, Autophagy, Reactive oxygen species, Permeability transition pore, Calcium, ATP, Membrane potential