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Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration.
- Source :
-
Nature cell biology [Nat Cell Biol] 2012 Apr 29; Vol. 14 (6), pp. 575-83. Date of Electronic Publication: 2012 Apr 29. - Publication Year :
- 2012
-
Abstract
- MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, we report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, an MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to facilitate normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure and maintenance of oligomeric ATP synthase. Our results provide insight into how the surprisingly diverse salutary functions of MCL-1 may control the survival of both normal and cancer cells.
- Subjects :
- Adenosine Triphosphate biosynthesis
Animals
Apoptosis
Cell Respiration
Cells, Cultured
Humans
Membrane Potentials
Mice
Microscopy, Electron, Transmission
Mitochondria ultrastructure
Myeloid Cell Leukemia Sequence 1 Protein
Proto-Oncogene Proteins c-bcl-2 genetics
Proton-Translocating ATPases metabolism
Mitochondria metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4679
- Volume :
- 14
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Nature cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 22544066
- Full Text :
- https://doi.org/10.1038/ncb2488