Alterations in the heart mitochondrial proteome in a desmin null heart failure model

Fountoulakis, Michael; Soumaka, Elisavet; Rapti, Kleopatra; Mavroidis, Manolis; Tsangaris, George Th.; Maris, Antony; Weisleder, Noah; Capetanaki, Yassemi

doi:10.1016/j.yjmcc.2004.12.008

Cited by 62 publications

(59 citation statements)

References 74 publications

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“…This proximity allows the desmin scaffold, together with αΒ-crystallin, to facilitate directed protein and metabolite targeting to mitochondria. As shown here, and as previously suggested by others (Fountoulakis et al, 2005;Martindale et al, 2005;Maloyan et al, 2005), αB-crystallin does localize in and outside of mitochondria, and thus, could support multiple processes. The potential compensatory interplay between desmin and αΒ-crystallin is further supported by the fact that both of them associate with important mitochondrial proteins.…”

Section: αB-crystallin and Desmin -Old Partners In A New Gamesupporting

confidence: 88%

“…αΒ-crystallin associates with all three cytoskeletal networks -microfilaments (Bennardini et al, 1992;Singh et al, 2007), microtubules (Arai and Atomi, 1997;Houck and Clark, 2010) and intermediate filaments (Nicholl and Quinlan, 1994;Iwaki et al, 1989;Wisniewski and Goldman, 1998) (reviewed in Wettstein et al, 2012) -and specifically desmin (Bennardini et al, 1992;Nicholl and Quinlan, 1994;Perng et al, 1999). There is also evidence that a fraction of αΒ-crystallin is located in mitochondria (Fountoulakis et al, 2005;Martindale et al, 2005;Maloyan et al, 2005;Mitra et al, 2013); however, its role there is not completely understood.…”

Section: Introductionmentioning

confidence: 99%

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

Diokmetzidou

Soumaka

Kloukina

et al. 2016

Journal of Cell Science

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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 (Δψ m ). 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.

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Section: αB-crystallin and Desmin -Old Partners In A New Gamesupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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

Diokmetzidou

Soumaka

Kloukina

et al. 2016

Journal of Cell Science

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“…The link between mitochondrial dysfunction and desminopathy is reflected by defects in mitochondrial morphology, positioning, and respiratory enzyme function in the desmin knockout mouse 45, 46, 47. In the present study, we show that desminopathy is associated with aberrant mitochondrial fission and increased expression of mitochondrial fission regulatory proteins both in vivo and in vitro using D7‐Des expression systems.…”

Section: Discussionsupporting

confidence: 58%

Aberrant Mitochondrial Fission Is Maladaptive in Desmin Mutation–Induced Cardiac Proteotoxicity

Alam

Abdullah

Aishwarya

et al. 2018

JAHA

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BackgroundDesmin filament proteins interlink the contractile myofibrillar apparatus with mitochondria, nuclei and the sarcolemma. Mutations in the human desmin gene cause cardiac disease, remodeling, and heart failure but the pathophysiological mechanisms remain unknown.Methods and ResultsCardiomyocyte‐specific overexpression of mutated desmin (a 7 amino acid deletion R172‐E178, D7‐Des Tg) causes accumulations of electron‐dense aggregates and myofibrillar degeneration associated with cardiac dysfunction. Though extensive studies demonstrated that these altered ultrastructural changes cause impairment of cardiac contractility, the molecular mechanism of cardiomyocyte death remains elusive. In the present study, we report that the D7‐Des Tg mouse hearts undergo aberrant mitochondrial fission associated with increased expression of mitochondrial fission regulatory proteins. Mitochondria isolated from D7‐Des Tg hearts showed decreased mitochondrial respiration and increased apoptotic cell death. Overexpression of mutant desmin by adenoviral infection in cultured cardiomyocytes led to increased mitochondrial fission, inhibition of mitochondrial respiration, and activation of cellular toxicity. Inhibition of mitochondrial fission by mitochondrial division inhibitor mdivi‐1 significantly improved mitochondrial respiration and inhibited cellular toxicity associated with D7‐Des overexpression in cardiomyocytes.ConclusionsAberrant mitochondrial fission results in mitochondrial respiratory defects and apoptotic cell death in D7‐Des Tg hearts. Inhibition of aberrant mitochondrial fission using mitochondrial division inhibitor significantly preserved mitochondrial function and decreased apoptotic cell death. Taken together, our study shows that maladaptive aberrant mitochondrial fission causes desminopathy‐associated cellular dysfunction.

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“…After fixing and washing steps, gels were kept in staining solution for 4 days, to achieve optimal staining. Similar staining recipes, sometimes slightly shortened, have also been used for establishing protein maps [20][21][22] or for monitoring protein level changes [23].…”

Section: Staining In Gelsmentioning

confidence: 99%

Protein stains for proteomic applications:Which, when, why?

Crawford²,

2006

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This review recollects literature data on sensitivity and dynamic range for the most commonly used colorimetric and fluorescent dyes for general protein staining, and summarizes procedures for the most common PTM-specific detection methods. It also compiles some important points to be considered in imaging and evaluation. In addition to theoretical considerations, examples are provided to illustrate differential staining of specific proteins with different detection methods. This includes a large body of original data on the comparative evaluation of several pre-and post-electrophoresis stains used in parallel on a single specimen, horse serum run in 2-DE (IPG-DALT). A number of proteins/protein spots are found to be over-or under-revealed with some of the staining procedures.

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Alterations in the heart mitochondrial proteome in a desmin null heart failure model

Cited by 62 publications

References 74 publications

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

Aberrant Mitochondrial Fission Is Maladaptive in Desmin Mutation–Induced Cardiac Proteotoxicity

Protein stains for proteomic applications:Which, when, why?

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