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Dissociating the dual roles of apoptosis‐inducing factor in maintaining mitochondrial structure and apoptosis
Author(s) -
Cheung Eric CC,
Joza Nicholas,
Steenaart Nancy AE,
McClellan Kelly A,
Neuspiel Margaret,
McNamara Stephen,
MacLaurin Jason G,
Rippstein Peter,
Park David S,
Shore Gordon C,
McBride Heidi M,
Penninger Josef M,
Slack Ruth S
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601276
Subject(s) - biology , apoptosis , microbiology and biotechnology , dual (grammatical number) , mitochondrion , apoptosis inducing factor , genetics , programmed cell death , caspase , art , literature
The mitochondrial protein apoptosis‐inducing factor (AIF) translocates to the nucleus and induces apoptosis. Recent studies, however, have indicated the importance of AIF for survival in mitochondria. In the absence of a means to dissociate these two functions, the precise roles of AIF remain unclear. Here, we dissociate these dual roles using mitochondrially anchored AIF that cannot be released during apoptosis. Forebrain‐specific AIF null (tel. Aif Δ ) mice have defective cortical development and reduced neuronal survival due to defects in mitochondrial respiration. Mitochondria in AIF deficient neurons are fragmented with aberrant cristae, indicating a novel role of AIF in controlling mitochondrial structure. While tel . Aif Δ Apaf1 −/− neurons remain sensitive to DNA damage, mitochondrially anchored AIF expression in these cells significantly enhanced survival. AIF mutants that cannot translocate into nucleus failed to induce cell death. These results indicate that the proapoptotic role of AIF can be uncoupled from its physiological function. Cell death induced by AIF is through its proapoptotic activity once it is translocated to the nucleus, not due to the loss of AIF from the mitochondria.

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