Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

Ramaccini, Daniela; Montoya-Uribe, Vanessa; Aan, Femke J.; Modesti, Lorenzo; Potes, Yaiza; Wieckowski, Mariusz R.; Krga, Irèna; Glibetić, Marija; Pinton, Paolo; Giorgi, Carlotta; Matter, Michelle L.

doi:10.3389/fcell.2020.624216

Cited by 80 publications

(66 citation statements)

References 260 publications

(358 reference statements)

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“…Only PNM have high mobility and are probably involved in transcription and translation. IMF are in continuous interaction with the sarcoplasmic reticulum to allow optimal buffering energy transfer (see in [183]). Therefore, disturbances in the intracellular distribution of mitochondria might result in impairment of heart contractile function.…”

Section: Gsk3β-cytoskeleton Interplay In Mitochondria Traffickingmentioning

confidence: 99%

GSK3 as a Regulator of Cytoskeleton Architecture: Consequences for Health and Disease

Hajka

Budziak

Pietras

et al. 2021

Cells

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Glycogen synthase kinase 3 (GSK3) was initially isolated as a critical protein in energy metabolism. However, subsequent studies indicate that GSK-3 is a multi-tasking kinase that links numerous signaling pathways in a cell and plays a vital role in the regulation of many aspects of cellular physiology. As a regulator of actin and tubulin cytoskeleton, GSK3 influences processes of cell polarization, interaction with the extracellular matrix, and directional migration of cells and their organelles during the growth and development of an animal organism. In this review, the roles of GSK3–cytoskeleton interactions in brain development and pathology, migration of healthy and cancer cells, and in cellular trafficking of mitochondria will be discussed.

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Section: Gsk3β-cytoskeleton Interplay In Mitochondria Traffickingmentioning

confidence: 99%

GSK3 as a Regulator of Cytoskeleton Architecture: Consequences for Health and Disease

Hajka

Budziak

Pietras

et al. 2021

Cells

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“…Although the details of the underlying intracellular signals were not identified, it is important to note that myosin expression was restored with the enhancement of ANT-1 and ATP levels. The correlation between myocardial contractile force and the structural units of myosin has been studied, and a decrease in the expression or mutations in myosin and mitochondrial gene have been shown to directly cause cardiac dysfunction [ 13 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model

Mori

Miyagawa

Kido

et al. 2021

Regenerative Therapy

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Introduction Idiopathic dilated cardiomyopathy (DCM) is associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. Mesenchymal stem cells (MSCs) can ameliorate distressed mitochondrial and structural proteins, as well as fibrosis, via the paracrine effect of cytokines. This study aimed to investigate whether the transplantation of adipose tissue-derived MSCs (ADSCs) reverses histological and functional abnormalities in the distressed myocardium of DCM-like hamsters by modulating the expression of adenine nucleotide translocase 1 (ANT-1). Methods Eighteen weeks after birth, ADSCs were implanted onto the cardiac surface of δ-sarcoglycan (SG)-deficient hamsters or sham surgery was performed. Results Left ventricular ejection fraction and end-systolic diameter were maintained in ADSC-treated animals for four weeks, ATP concentration was considerably elevated in the cardiomyocytes of these animals, and ANT-1 expression was significantly upregulated as well. The expression of extracellular matrix and myocardial cytoskeletal proteins, such as collagen, SG, and α-dystroglycan, did not differ between groups. However, significant improvements in myosin and Smad4 expression, cardiomyocyte hypertrophy, and capillary density occurred in the ADSC-treated group. Conclusions We demonstrated that ADSCs might maintain cardiac function in the DCM hamster model by enhancing ATP concentration, as well as mitochondrial transporter and myosin expression, indicating their potential for DCM treatment.

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“…Of all the disorders discussed, those that seem to most drastically affect proteins related to OXPHOS, such as DCMA, MGCA9 and COXPD31, frequently present with cardiomyopathy. OXPHOS dysfunction can lead to oxidative stress and subsequent increases in ROS production, which is commonly associated with cardiomyopathy [ 129 ]. Maintenance of mitochondrial proteostasis is particularly important for cellular energy production as the import, processing, and folding of incoming proteins is required for the proper formation of respiratory chain complexes [ 74 ].…”

Section: Cellular Responses To Abnormal Mitochondrial Proteostasismentioning

confidence: 99%

“…A disruption of mitochondrial proteostasis can cause significant disruptions in ATP production and lead to oxidative stress and the accumulation of toxic ROS [ 130 ]. Injury to mitochondria through oxidative stress also leads to alterations in mitochondrial fission and fusion dynamics, leading to excessive mitophagy which plays a role in cardiomyopathy and heart failure [ 129 , 130 , 131 ]. Mouse models that abrogate mitochondrial fission and fusion show that this ultimately leads to complete failure of heart function [ 132 ].…”

Section: Cellular Responses To Abnormal Mitochondrial Proteostasismentioning

confidence: 99%

Mitochondrial Protein Homeostasis and Cardiomyopathy

Wachoski-Dark

Zhao

Khan

et al. 2022

IJMS

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Human mitochondrial disorders impact tissues with high energetic demands and can be associated with cardiac muscle disease (cardiomyopathy) and early mortality. However, the mechanistic link between mitochondrial disease and the development of cardiomyopathy is frequently unclear. In addition, there is often marked phenotypic heterogeneity between patients, even between those with the same genetic variant, which is also not well understood. Several of the mitochondrial cardiomyopathies are related to defects in the maintenance of mitochondrial protein homeostasis, or proteostasis. This essential process involves the importing, sorting, folding and degradation of preproteins into fully functional mature structures inside mitochondria. Disrupted mitochondrial proteostasis interferes with mitochondrial energetics and ATP production, which can directly impact cardiac function. An inability to maintain proteostasis can result in mitochondrial dysfunction and subsequent mitophagy or even apoptosis. We review the known mitochondrial diseases that have been associated with cardiomyopathy and which arise from mutations in genes that are important for mitochondrial proteostasis. Genes discussed include DnaJ heat shock protein family member C19 (DNAJC19), mitochondrial import inner membrane translocase subunit TIM16 (MAGMAS), translocase of the inner mitochondrial membrane 50 (TIMM50), mitochondrial intermediate peptidase (MIPEP), X-prolyl-aminopeptidase 3 (XPNPEP3), HtraA serine peptidase 2 (HTRA2), caseinolytic mitochondrial peptidase chaperone subunit B (CLPB) and heat shock 60-kD protein 1 (HSPD1). The identification and description of disorders with a shared mechanism of disease may provide further insights into the disease process and assist with the identification of potential therapeutics.

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Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

Cited by 80 publications

References 260 publications

GSK3 as a Regulator of Cytoskeleton Architecture: Consequences for Health and Disease

GSK3 as a Regulator of Cytoskeleton Architecture: Consequences for Health and Disease

Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model

Mitochondrial Protein Homeostasis and Cardiomyopathy

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