| First Author | Diokmetzidou A | Year | 2016 |
| Journal | J Cell Sci | Volume | 129 |
| Issue | 20 | Pages | 3705-3720 |
| PubMed ID | 27566162 | Mgi Jnum | J:246650 |
| Mgi Id | MGI:5924418 | Doi | 10.1242/jcs.192203 |
| Citation | Diokmetzidou A, et al. (2016) Desmin and alphaB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival. J Cell Sci 129(20):3705-3720 |
| abstractText | The association of desmin with the alpha-crystallin Beta-chain (alphaBeta-crystallin; encoded by CRYAB), and the fact that mutations in either one of them leads to heart failure in humans and mice, suggests a potential compensatory interplay between the two in cardioprotection. To address this hypothesis, we investigated the consequences of alphaBeta-crystallin overexpression in the desmin-deficient (Des-/-) mouse model, which possesses a combination of the pathologies found in most cardiomyopathies, with mitochondrial defects as a hallmark. We demonstrated that cardiac-specific alphaBeta-crystallin overexpression ameliorates all these defects and improves cardiac function to almost wild-type levels. Protection by alphaBeta-crystallin overexpression is linked to maintenance of proper mitochondrial protein levels, inhibition of abnormal mitochondrial permeability transition pore activation and maintenance of mitochondrial membrane potential (Deltapsim). Furthermore, we found that both desmin and alphaBeta-crystallin are localized at sarcoplasmic reticulum (SR)-mitochondria-associated membranes (MAMs), where they interact with VDAC, Mic60 - the core component of mitochondrial contact site and cristae organizing system (MICOS) complex - and ATP synthase, suggesting that these associations could be crucial in mitoprotection at different levels. |
