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Publication
Bid maintains mitochondrial cristae structure and function and protects against
cardiac disease in an integrative genomics study.
Authors Salisbury-Ruf CT, Bertram CC, Vergeade A, Lark DS, Shi Q, Heberling ML, Fortune
NL, Okoye GD, Jerome WG, Wells QS, Fessel J, Moslehi J, Chen H, Roberts LJ,
Boutaud O, Gamazon ER, Zinkel SS
Submitted By Submitted Externally on 11/16/2018
Status Published
Journal eLife
Year 2018
Date Published 10/1/2018
Volume : Pages 7 : Not Specified
PubMed Reference 30281024
Abstract Bcl-2 family proteins reorganize mitochondrial membranes during apoptosis, to
form pores and rearrange cristae. In vitro and in vivo analysis integrated with
human genetics reveals a novel homeostatic mitochondrial function for Bcl-2
family protein Bid. Loss of full-length Bid results in apoptosis-independent,
irregular cristae with decreased respiration. Bid-/- mice display stress-induced
myocardial dysfunction and damage. A gene-based approach applied to a biobank,
validated in two independent GWAS studies, reveals that decreased genetically
determined BID expression associates with myocardial infarction (MI)
susceptibility. Patients in the bottom 5% of the expression distribution exhibit
>4 fold increased MI risk. Carrier status with nonsynonymous variation in Bid's
membrane binding domain, BidM148T, associates with MI predisposition.
Furthermore, Bid but not BidM148T associates with Mcl-1Matrix, previously
implicated in cristae stability; decreased MCL-1 expression associates with MI.
Our results identify a role for Bid in homeostatic mitochondrial cristae
reorganization, that we link to human cardiac disease.




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