title: BCL-2 improves oxidative phosphorylation and modulates adenine nucleotide translocation in mitochondria of cells harboring mutant mtDNA.
abstract: Members of the BCL-2-related antiapoptotic family of proteins have been shown previously to regulate ATP/ADP exchange across the mitochondrial membranes and to prevent the loss of coupled mitochondrial respiration during apoptosis. We have found that BCL-2/BCL-x(L) can also improve mitochondrial oxidative phosphorylation in cells harboring pathogenic mutations in mitochondrial tRNA genes. The effect of BCL-2 overexpression in mutated cells was independent from apoptosis and was presumably associated with a modulation of adenine nucleotide exchange between mitochondria and cytosol. These results suggest that BCL-2 can regulate respiratory functions in response to mitochondrial distress by regulating the levels of adenine nucleotides.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA. gim2004@mail.med.cornell.edu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Manfredi
authors.forename: Jennifer Q
authors.initials: JQ
authors.lastname: Kwong
authors.forename: José A
authors.initials: JA
authors.lastname: Oca-Cossio
authors.forename: Markus
authors.initials: M
authors.lastname: Woischnik
authors.forename: Carl D
authors.initials: CD
authors.lastname: Gajewski
authors.forename: Katherine
authors.initials: K
authors.lastname: Martushova
authors.forename: Marilena
authors.initials: M
authors.lastname: D'Aurelio
authors.forename: Avi L
authors.initials: AL
authors.lastname: Friedlich
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Moraes
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001859:Bone Neoplasms; D003600:Cytosol / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D012516:Osteosarcoma; D010085:Oxidative Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: D000227:Adenine Nucleotides; C494811:BCL2L1 protein, human; D004272:DNA, Mitochondrial; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D000226:Mitochondrial ADP, ATP Translocases