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  • Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival.

Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival.

Journal of cell science (2016-08-28)
Antigoni Diokmetzidou, Elisavet Soumaka, Ismini Kloukina, Mary Tsikitis, Manousos Makridakis, Aimilia Varela, Constantinos H Davos, Spiros Georgopoulos, Vasiliki Anesti, Antonia Vlahou, Yassemi Capetanaki
ABSTRACT

The association of desmin with the α-crystallin Β-chain (αΒ-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 αΒ-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 αΒ-crystallin overexpression ameliorates all these defects and improves cardiac function to almost wild-type levels. Protection by αΒ-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 (Δψm). Furthermore, we found that both desmin and αΒ-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.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Anti-Mitofusin 2 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Tetramethylrhodamine methyl ester perchlorate, ≥95%