In:
Journal of Cell Biology, Rockefeller University Press, Vol. 195, No. 2 ( 2011-10-17), p. 263-276
Abstract:
Mammalian Bcl-xL protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced outer membrane permeabilization. Contrary to expectation, we found by electron microscopy and biochemical approaches that endogenous Bcl-xL also localized to inner mitochondrial cristae. Two-photon microscopy of cultured neurons revealed large fluctuations in inner mitochondrial membrane potential when Bcl-xL was genetically deleted or pharmacologically inhibited, indicating increased total ion flux into and out of mitochondria. Computational, biochemical, and genetic evidence indicated that Bcl-xL reduces futile ion flux across the inner mitochondrial membrane to prevent a wasteful drain on cellular resources, thereby preventing an energetic crisis during stress. Given that F1FO–ATP synthase directly affects mitochondrial membrane potential and having identified the mitochondrial ATP synthase β subunit in a screen for Bcl-xL–binding partners, we tested and found that Bcl-xL failed to protect β subunit–deficient yeast. Thus, by bolstering mitochondrial energetic capacity, Bcl-xL may contribute importantly to cell survival independently of other Bcl-2 family proteins.
Type of Medium:
Online Resource
ISSN:
1540-8140
,
0021-9525
DOI:
10.1083/jcb.201108059
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2011
detail.hit.zdb_id:
1421310-2
SSG:
12
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