A systematic review of post-translational modifications in the mitochondrial permeability transition pore complex associated with cardiac diseases

Alves-Figueiredo, Hugo; Silva-Platas, Christian; Lozano, Omar; Vázquez‐Garza, Eduardo; Guerrero-Beltrán, Carlos Enrique; Zarain‐Herzberg, Ángel; García‐Rivas, Gerardo

doi:10.1016/j.bbadis.2020.165992

Cited by 17 publications

(11 citation statements)

References 213 publications

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“…The presence of reactive oxygen species around mitochondria in the cell can oxidize protein thiols in the vicinity, so thiol modification could be significant for catalysis under physiological conditions. Further development and application of chemical methods to detect, distinguish, and time modify cysteines in the cell or tissues would allow better understanding of any consequences from modifications of cysteines in MAO [119,125,126].…”

Section: Does the Oxidation Of Mao Thiols Have Any Importance In Vivo?mentioning

confidence: 99%

Questions in the Chemical Enzymology of MAO

Ramsay

Albreht

2021

Chemistry

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We have structure, a wealth of kinetic data, thousands of chemical ligands and clinical information for the effects of a range of drugs on monoamine oxidase activity in vivo. We have comparative information from various species and mutations on kinetics and effects of inhibition. Nevertheless, there are what seem like simple questions still to be answered. This article presents a brief summary of existing experimental evidence the background and poses questions that remain intriguing for chemists and biochemists researching the chemical enzymology of and drug design for monoamine oxidases (FAD-containing EC 4.1.3.4).

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Section: Does the Oxidation Of Mao Thiols Have Any Importance In Vivo?mentioning

confidence: 99%

Questions in the Chemical Enzymology of MAO

Ramsay

Albreht

2021

Chemistry

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“…Diabetic patients exhibit increased cardiac fatty acid utilization, changed glucose uptake and oxidation and increased fructose content, which may lead to mitochondrial structural remodelling and accelerate O‐GlcNAylation and AGEs formation 107,121,122,123 . Besides, a number of PTMs can alter the function of the mitochondrial permeability transition pore (mPTP) opening, affect energy metabolism and indirectly participate in the pathophysiology process of DCM 124 . Among the various PTMs, phosphorylation and acetylation are overwhelmingly dominant 124 .…”

Section: Discussionmentioning

confidence: 99%

Post‐translational modifications in diabetic cardiomyopathy

Li,

Chen,

Huang

et al. 2024

J Cellular Molecular Medi

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The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling the pathogenesis of diabetic cardiomyopathy, with a particular emphasis on investigating various post‐translational modifications. These modifications dynamically regulate protein function in response to changes in the internal and external environment, and their disturbance of homeostasis holds significant relevance for the development of chronic ailments. This review provides a comprehensive overview of the common post‐translational modifications involved in the initiation and progression of diabetic cardiomyopathy, including O‐GlcNAcylation, phosphorylation, methylation, acetylation and ubiquitination. Additionally, the review discusses drug development strategies for targeting key post‐translational modification targets, such as agonists, inhibitors and PROTAC (proteolysis targeting chimaera) technology that targets E3 ubiquitin ligases.

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“…Protein post-translational modifications (PTMs) were found to contribute to heart failure progression by regulating mitochondrial function [ 259 ]. Of the many proteins regulated by PTMs, mPTP is gaining attention as a potential mechanism underlying mitochondrial dysfunction and has as many as 55 PTM sites [ 260 ]. It is, therefore, possible that PTM of mPTP may contribute to mitochondrial toxicity in the heart.…”

Section: Main Properties Of Mitochondria and Drug-induced Mitochondri...mentioning

confidence: 99%

Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation

Tang

Wang

et al. 2022

Pharmaceutics

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Drug-induced cardiotoxicity not only leads to the attrition of drugs during development, but also contributes to the high morbidity and mortality rates of cardiovascular diseases. Comprehensive testing for proarrhythmic risks of drugs has been applied in preclinical cardiac safety assessment for over 15 years. However, other mechanisms of cardiac toxicity have not received such attention. Of them, mitochondrial impairment is a common form of cardiotoxicity and is known to account for over half of cardiovascular adverse-event-related black box warnings imposed by the U.S. Food and Drug Administration. Although it has been studied in great depth, mitochondrial toxicity assessment has not yet been incorporated into routine safety tests for cardiotoxicity at the preclinical stage. This review discusses the main characteristics of mitochondria in cardiomyocytes, drug-induced mitochondrial toxicities, and high-throughput screening strategies for cardiomyocytes, as well as their proposed integration into preclinical safety pharmacology. We emphasize the advantages of using adult human primary cardiomyocytes for the evaluation of mitochondrial morphology and function, and the need for a novel cardiac safety testing platform integrating mitochondrial toxicity and proarrhythmic risk assessments in cardiac safety evaluation.

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A systematic review of post-translational modifications in the mitochondrial permeability transition pore complex associated with cardiac diseases

Cited by 17 publications

References 213 publications

Questions in the Chemical Enzymology of MAO

Questions in the Chemical Enzymology of MAO

Post‐translational modifications in diabetic cardiomyopathy

Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation

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