title: Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival.
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.
authors: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Antigoni
authors: A
authors: Diokmetzidou
authors: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Elisavet
authors: 0000-0001-8705-6741
authors: E
authors: Soumaka
authors: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Ismini
authors: I
authors: Kloukina
authors: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Mary
authors: M
authors: Tsikitis
authors: Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Manousos
authors: M
authors: Makridakis
authors: Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Aimilia
authors: A
authors: Varela
authors: Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Constantinos H
authors: CH
authors: Davos
authors: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Spiros
authors: S
authors: Georgopoulos
authors: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Vasiliki
authors: V
authors: Anesti
authors: Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece.
authors: Antonia
authors: A
authors: Vlahou
authors: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 11527, Greece ycapetanaki@bioacademy.gr.
authors: Yassemi
authors: 0000-0002-3089-0767
authors: Y
authors: Capetanaki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003893:Desmin / Q000172:deficiency / Q000378:metabolism*; D006334:Heart Function Tests; D006706:Homeostasis / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010805:Physical Conditioning, Animal; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D013550:Swimming; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D003893:Desmin; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D050994:Voltage-Dependent Anion Channels; D038203:alpha-Crystallin B Chain
keywords: Cristae; Cytoskeleton; Heart failure; Intermediate filaments; MAMs; Mitochondria; Small heat-shock protein