VDAC2 as a novel target for heart failure: Ca2+ at the sarcomere, mitochondria and SR

Rosenberg, Paul B.

doi:10.1016/j.ceca.2022.102586

Cited by 9 publications

(9 citation statements)

References 112 publications

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“…VDAC1 inhibition significantly attenuated mitochondrial Ca 2+ overload and protected cells from hypoxia-reoxygenation (H/O) ( 58 ). Cardiac VDAC2 knockout mice showed decreased ejection fraction and increased brain natriuretic peptide (BNP) level and cardiac fibrosis, which was consistent with DCM features ( 56 ).…”

Section: Introductionmentioning

confidence: 79%

“…Adult cardiac deletion of a multifunctional regulator GSK-3 contributed to severe DCM due to cell cycle dysregulation, indicating that GSK-3 is involved in maintaining cardiac homeostasis ( 49 , 55 ). VDAC, the most abundant mitochondrial outer membrane protein, contains three subtypes-VDAC 1, 2, and 3 in mammalian cells ( 56 ). It has been reported that VDAC1 is upregulated in the left ventricle of HCM patients ( 57 ).…”

Section: Introductionmentioning

confidence: 99%

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Mitochondria-associated endoplasmic reticulum membranes (MAMs): Possible therapeutic targets in heart failure

Yao

Zhang

Wang

et al. 2023

Front. Cardiovasc. Med.

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Mitochondria-associated endoplasmic reticulum membranes (MAMs) are formed by physical connections of the endoplasmic reticulum and mitochondria. Over the past decades, great breakthroughs have been made in the study of ER-mitochondria communications. It has been identified that MAM compartments are pivotal in regulating neurological function. Accumulating studies indicated that MAMs participate in the development of cardiovascular diseases. However, the specific role of MAMs in heart failure remains to be fully understood. In this article, we first summarize the structural and functional properties of MAM and MAM-associated proteins. We then focus on the roles of MAMs in myocardial infarction, cardiomyopathy and heart failure, and discuss the involvement of MAMs in disease progression and treatment. Elucidating these issues may provide important insights into therapeutic intervention of heart failure.

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Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Mitochondria-associated endoplasmic reticulum membranes (MAMs): Possible therapeutic targets in heart failure

Yao

Zhang

Wang

et al. 2023

Front. Cardiovasc. Med.

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“…TSPO has been shown to influence the activity of other mitochondrial components, such as the mPTP, VDAC, and inner membrane anion channel (IMAC), that play a crucial role in determining the fate of cardiomyocytes in acute and chronic CDs, such as acute MI and HF. 39,40 2.2.1. mPTP. The mPTP supramolecular complex is a nonspecific channel with a cutoff of 1.5 kDa that is formed and opens under stress conditions, triggering the so-called mitochondrial permeability transition that is responsible for cardiomyocyte death.…”

Section: The Role Of Tspo In Cardiac Pathophysiologymentioning

confidence: 99%

Section: The Role Of Tspo In Cardiac Pathophysiologymentioning

confidence: 99%

Targeting the Translocator Protein (18 kDa) in Cardiac Diseases: State of the Art and Future Opportunities

Baglini,

Poggetti,

Cavallini

et al. 2023

J. Med. Chem.

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Mitochondria dysfunctions are typical hallmarks of cardiac disorders (CDs). The multiple tasks of this energy-producing organelle are well documented, but its pathophysiologic involvement in several manifestations of heart diseases, such as altered electromechanical coupling, excitability, and arrhythmias, is still under investigation. The human 18 kDa translocator protein (TSPO) is a protein located on the outer mitochondrial membrane whose expression is altered in different pathological conditions, including CDs, making it an attractive therapeutic and diagnostic target. Currently, only a few TSPO ligands are employed in CDs and cardiac imaging. In this Perspective, we report an overview of the emerging role of TSPO at the heart level, focusing on the recent literature concerning the development of TSPO ligands used for fighting and imaging heart-related disease conditions. Accordingly, targeting TSPO might represent a successful strategy to achieve novel therapeutic and diagnostic strategies to unravel the fundamental mechanisms and to provide solutions to still unanswered questions in CDs.

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“…Since hVDAC2 promotes cancer cell survival, small molecule inhibitors that disrupt hVDAC2 function are being explored for cancer therapy [10] . hVDAC2 is also a promising candidate for neurodegenerative diseases, including heart failure, [9b,11] amyotrophic lateral sclerosis, [12] hypoxia, [13] epilepsy, [14] Parkinson's [15] and Alzheimer's disease [16] . However, our limited knowledge of this specific isoform has severely hindered the design and development of peptidomimetics and small molecule inhibitors for VDAC2 functional modulation.…”

Section: Introductionmentioning

confidence: 99%

Photoradical‐Mediated Catalyst‐Independent Protein Cross‐Link with Unusual Fluorescence Properties

Bora

Mahalakshmi

2023

ChemBioChem

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Photo‐actively modified natural amino acids have served as lucrative probes for precise mapping of the dynamics, interaction networks, and turnover of cytosolic proteins both in vivo and ex vivo. In our attempts to extend the utility of photoreactive reporters to map the molecular characteristics of vital membrane proteins, we carried out site‐selective incorporation of 7‐fluoro‐indole in the human mitochondrial outer membrane protein VDAC2 (voltage‐dependent anion channel isoform 2), with the aim of generating Trp−Phe/Tyr cross‐links. Prolonged irradiation at 282 nm provided us with a surprisingly unusual fluorophore that displayed sizably red‐shifted excitation (λex‐max=280 nm→360 nm) and emission (λem‐max=330 nm→430 nm) spectra that was reversible with organic solvents. By measuring the kinetics of the photo‐activated cross‐linking with a library of hVDAC2 variants, we demonstrate that formation of this unusual fluorophore is kinetically retarded, independent of tryptophan, and is site‐specific. Using other membrane (Tom40 and Sam50) and cytosolic (MscR and DNA Pol I) proteins, we additionally show that formation of this fluorophore is protein‐independent. Our findings reveal the photoradical‐mediated accumulation of reversible tyrosine cross‐links, with unusual fluorescent properties. Our findings have immediate applications in protein biochemistry and UV‐mediated protein aggregation and cellular damage, opening avenues for formulating therapeutics that prolong cell viability in humans.

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VDAC2 as a novel target for heart failure: Ca2+ at the sarcomere, mitochondria and SR

Cited by 9 publications

References 112 publications

Mitochondria-associated endoplasmic reticulum membranes (MAMs): Possible therapeutic targets in heart failure

Mitochondria-associated endoplasmic reticulum membranes (MAMs): Possible therapeutic targets in heart failure

Targeting the Translocator Protein (18 kDa) in Cardiac Diseases: State of the Art and Future Opportunities

Photoradical‐Mediated Catalyst‐Independent Protein Cross‐Link with Unusual Fluorescence Properties

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