Abstract
The regulation of mitochondrial permeability transition (MPT) is essential for cell survival. Un-controlled opening of the MPT pore is often associated with cell death. Anti-death protein Bcl-2 can block MPT as assessed by the enhanced capacity of mitochondria to accumulate and retain Ca2+. We report here that two proteins of the mitochondrial fission machinery, dynamin-related protein (Drp1) and human mitochondrial fission protein (hFis1), have an antagonistic effect on Bcl-2. Drp1, with the assistance of hFis1, sensitizes cells to MPT by reducing the mitochondrial Ca2+ retention capacity (CRC). While the reduction of CRC by Drp1/hFis1 is linked to mitochondrial fission, the antagonism between Bcl-2 and Drp1 appears to be mediated by mutually exclusive interactions of the two proteins with hFis1. The complexity of protein-protein interactions demonstrated in the present study suggests that in addition to the previously described role of Bcl-2 in the control of apoptosis, Bcl-2 may also participate directly or indirectly in the regulation of mitochondrial fission.
Original language | English (US) |
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Pages (from-to) | 187-199 |
Number of pages | 13 |
Journal | Molecular and Cellular Biochemistry |
Volume | 272 |
Issue number | 1-2 |
DOIs | |
State | Published - Apr 2005 |
Externally published | Yes |
Keywords
- Apotosis
- Bcl-2
- Calcium
- Drp1
- Mitochondria
- Mitochondrial fission
- Permeability transition
- hFis1
ASJC Scopus subject areas
- Molecular Biology
- Clinical Biochemistry
- Cell Biology