| First Author | Salisbury-Ruf CT | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 30281024 | Mgi Jnum | J:268835 |
| Mgi Id | MGI:6269245 | Doi | 10.7554/eLife.40907 |
| Citation | Salisbury-Ruf CT, et al. (2018) Bid maintains mitochondrial cristae structure and function and protects against cardiac disease in an integrative genomics study. Elife 7:e40907 |
| abstractText | 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, Bid(M148T), associates with MI predisposition. Furthermore, Bid but not Bid(M148T) associates with Mcl-1(Matrix), 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. |
