BCL-2 improves oxidative phosphorylation and modulates adenine nucleotide translocation in mitochondria of cells harboring mutant mtDNA.
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.
Manfredi
Giovanni
G
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA. gim2004@mail.med.cornell.edu
Kwong
Jennifer Q
JQ
Oca-Cossio
José A
JA
Woischnik
Markus
M
Gajewski
Carl D
CD
Martushova
Katherine
K
D'Aurelio
Marilena
M
Friedlich
Avi L
AL
Moraes
Carlos T
CT
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
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