Bcl-2 Suppresses Oxidative Phosphorylation Defects Caused by Mitochondrial DNA Mutations

. The protooncogene Bcl-2 prevents apoptosis by still unknown mechanisms. Bcl-2 has been shown to localize to multiple cell compartments, but mainly to the mitochondria. Bcl-2 has been shown to prevent loss of mitochondrial membrane potential and activation of the mitochondrial permeability transition pore (1), which might be responsible for the activation of some apoptotic pathways. Mutations in the mitochondrial DNA (mtDNA) are associated with a heterogeneous group of sporadic or maternally inherited metabolic disorders. We have analyzed the effects of Bcl-2 overexpression in transmitochondrial cell lines (cybrids) harboring pathogenic mtDNA mutations, to investigate if the Bcl-2 protective effect on mitochondrial function could be extended to primary defects of the mitochondrial respiratory chain.