Disease Modeling of Mitochondrial Cardiomyopathy Using Patient-Specific Induced Pluripotent Stem Cells

SIMPLE SUMMARY: Mitochondria are essential intracellular organelles that generate energy within the cell. Mitochondria are present in all organs, and organs are powered by the energy produced by mitochondria. Mitochondria are composed of proteins encoded by nuclear and mitochondrial DNA. It is possible that mutations in nuclear and mitochondrial DNA cause alterations in proteins that make up mitochondria, resulting in mitochondrial dysfunction. Since cellular and organ functions depend on mitochondrial function, this mitochondrial dysfunction can lead to tissue dysfunction, namely mitochondrial diseases. In recent years, there have been many reports of the multifaceted functions of mitochondria. However, there is still little knowledge about the diseases. This problem arises because there is no suitable model to mimic mitochondrial diseases. In this paper, we introduce mitochondrial cardiomyopathy models that mimic patients’ cardiomyocytes using human induced pluripotent stem cells (iPSCs). The use of human iPSCs will advance the understanding of the pathogenesis of mitochondrial cardiomyopathy and the development of new drugs. ABSTRACT: Mitochondrial cardiomyopathy (MCM) is characterized as an oxidative phosphorylation disorder of the heart. More than 100 genetic variants in nuclear or mitochondrial DNA have been associated with MCM. However, the underlying molecular mechanisms linking genetic variants to MCM are not fully understood due to the lack of appropriate cellular and animal models. Patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) provide an attractive experimental platform for modeling cardiovascular diseases and predicting drug efficacy to such diseases. Here we introduce the pathological and therapeutic studies of MCM using iPSC-CMs and discuss the questions and latest strategies for research using iPSC-CMs.