| First Author | Weaver D | Year | 2014 |
| Journal | Mol Cell | Volume | 54 |
| Issue | 5 | Pages | 870-8 |
| PubMed ID | 24813948 | Mgi Jnum | J:215258 |
| Mgi Id | MGI:5604965 | Doi | 10.1016/j.molcel.2014.03.048 |
| Citation | Weaver D, et al. (2014) Distribution and apoptotic function of outer membrane proteins depend on mitochondrial fusion. Mol Cell 54(5):870-8 |
| abstractText | Cells deficient in mitochondrial fusion have been shown to have defects linked to the exchange of inner membrane and matrix components. Because outer-mitochondrial membrane (OMM) constituents insert directly from the cytoplasm, a role for fusion in their intermitochondrial transfer was unanticipated. Here, we show that fibroblasts lacking the GTPases responsible for OMM fusion, mitofusins 1 and 2 (MFN1 and MFN2), display more heterogeneous distribution of OMM proteins. Proteins with different modes of OMM association display varying degrees of heterogeneity in Mfn1/2(-/-) cells and different kinetics of transfer during fusion in fusion-competent cells. Proapoptotic Bak exhibits marked heterogeneity, which is normalized upon expression of MFN2. Bak is critical for Bid-induced OMM permeabilization and cytochrome c release, and Mfn1/2(-/-) cells show dysregulation of Bid-dependent apoptotic signaling. Bid sensitivity of Bak-deficient mitochondria is regained upon fusion with Bak-containing mitochondria. Thus, OMM protein distribution depends on mitochondrial fusion and is a locus of apoptotic dysfunction in conditions of fusion deficiency. |
