title: Mitochondria damage checkpoint, aging, and cancer.
abstract: There is growing evidence supporting the progressing decline in mitochondrial function with age. Mitochondria are the major site of reactive oxygen species (ROS) production in the cell; therefore it is likely that progressive decline in mitochondrial function is due to the accumulation of oxidative damage with age. Despite this notion, a role for mitochondria in cellular senescence has been largely ignored. Our studies using mitochondrial gene knockout cells (rho(0)) from a variety of tissue types demonstrate that loss of mitochondrial function leads to cell cycle arrest, cellular senescence, and tumorigenic phenotype. In light of these and earlier studies we hypothesize the existence of a mitochondria damage checkpoint (mitocheckpoint) in human cells. Mitocheckpoint permits cells to arrest in the cell cycle in order to repair/restore mitochondrial function to the normal level. Upon overwhelming, persistent, or severe damage to mitochondria, mitocheckpoint machinery may allow cells to undergo senescence. Thus cellular senescence may function as another checkpoint before cells decide to initiate programmed cell death resulting in aging of tissues and organs. Alternatively, mutations occur in the mitochondrial and/or nuclear DNA, resulting in tumorigenesis.
authors.affiliation: Department of Cancer Genetics, Cell and Virus Building, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. keshav.singh@roswellpark.org
authors.forename: Keshav K
authors.initials: KK
authors.lastname: Singh
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial