| Autor: |
Christi T Salisbury-Ruf, Clinton C Bertram, Aurelia Vergeade, Daniel S Lark, Qiong Shi, Marlene L Heberling, Niki L Fortune, G Donald Okoye, W Gray Jerome, Quinn S Wells, Josh Fessel, Javid Moslehi, Heidi Chen, L Jackson Roberts II, Olivier Boutaud, Eric R Gamazon, Sandra S Zinkel |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 7 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.40907 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
