Mitochondria, apoptosis and autoimmunity.
A functional immune system is dependent on the generation and selection of a lymphocyte repertoire that is sufficiently diverse to respond to innumerable foreign antigens yet be adequately self-tolerant to avoid the development of autoimmunity. Programmed cell death by a process known as apoptosis is responsible for negative selection of nonreactive leukocyte precursors and autoreactive thymocytes, killing of infected and transformed cells by cytotoxic lymphocytes and deletion of superfluous activated lymphocytes by activation-induced cell death (AICD) and peripheral deletion at the termination of an immune response. Mitochondrial respiration is required to meet the energy requirements of activated and proliferating peripheral lymphocytes. Several mitochondrial proteins have been implicated as regulators of apoptosis in the immune system that are required for prevention of autoimmunity. Recent discoveries have shed light on mitochondrial functions as they relate to cell death, including caspase-dependent and -independent apoptosis, mitochondrial death substrates and events that disable mitochondrial functions during apoptosis. These discoveries, taken with reports that the specific manner by which a cell dies greatly impacts on the nature of subsequent immune responses, highlight an exciting era of research on mitochondrial function and its role in apoptosis and the effects on immune responses.
Pinkoski
Michael J
MJ
Medical Research Council, Toxicology Unit, Leicester, UK. mp191@le.ac.uk
Waterhouse
Nigel J
NJ
Green
Douglas R
DR
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D002952:Citric Acid Cycle; D004579:Electron Transport; D006801:Humans; D007107:Immune System / Q000473:pathology; D008928:Mitochondria / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein