Mitochondrial liaisons of p53.
Mitochondria play a central role in cell survival and cell death. While producing the bulk of intracellular ATP, mitochondrial respiration represents the most prominent source of harmful reactive oxygen species. Mitochondria participate in many anabolic pathways, including cholesterol and nucleotide biosynthesis, yet also control multiple biochemical cascades that contribute to the programmed demise of cells. The tumor suppressor protein p53 is best known for its ability to orchestrate a transcriptional response to stress that can have multiple outcomes, including cell cycle arrest and cell death. p53-mediated tumor suppression, however, also involves transcription-independent mechanisms. Cytoplasmic p53 can physically interact with members of the BCL-2 protein family, thereby promoting mitochondrial membrane permeabilization. Moreover, extranuclear p53 can suppress autophagy, a major prosurvival mechanism that is activated in response to multiple stress conditions. Thirty years have passed since its discovery, and p53 has been ascribed with an ever-increasing number of functions. For instance, p53 has turned out to influence the cell's redox status, by transactivating either anti- or pro-oxidant factors, and to regulate the metabolic switch between glycolysis and aerobic respiration. In this review, we will analyze the mechanisms by which p53 affects the balance between the vital and lethal functions of mitochondria.
Galluzzi
Lorenzo
L
INSERM U848, Institut Gustave Roussy, Pavillon de Recherche 1, Villejuif (Paris), France.
Morselli
Eugenia
E
Kepp
Oliver
O
Vitale
Ilio
I
Pinti
Marcello
M
Kroemer
Guido
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53