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The molecular interrelationships between mitochondrial morphogenesis and apoptosis
Author(s) -
Youle Richard J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a96-c
Subject(s) - microbiology and biotechnology , mitochondrial apoptosis induced channel , mitochondrion , apoptosis , bacterial outer membrane , inner membrane , mitochondrial fusion , biology , inner mitochondrial membrane , dynamin , chemistry , cell , mitochondrial dna , biochemistry , gene , endocytosis , escherichia coli
During apoptosis the pro‐apoptotic members of the Bcl‐2 family, Bax and Bak, coalease into foci on the mitochondrial membrane at sites where mitochondria subsequently divide and close in time to the release of proteins from the mitochondrial inter‐membrane space. Inhibition of the normal mitochondrial division machinery delays cytochome c release and the cell death process itself. We have studied an endophilin isoform that binds to Bax and, along with the dynamin related protein, Drp1, is specifically involved in coupling the outer mitochondrial membrane (OMM) to the inner membrane. Using RNA interference (RNAi) to deplete endophilin B1 followed by immunofluorescence microscopy we detect separation of the inner mitochondrial membrane and the outer membrane and the formation of long tubules of OMM stemming from mitochondria. We also find that cells lacking Bax and Bak have decreased mitochondrial fusion and altered mitochondrial morphology linking Bax and Bak to mitochondrial morphogenesis in healthy cells. Interestingly, endophilin B1 binds to Bax during apoptosis and translocates to mitochondria. Results on the mechanism and consequence of Bax binding to endophilin B1 will be presented and how endophilin B1 couples Bax to normal mitochondrial morphogenesis and to apoptosis will be discussed.