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

Tokuyama, Takeshi; Ahmed, Razan Elfadil; Chanthra, Nawin; Anzai, Tatsuya; Uosaki, Hideki

doi:10.3390/biology10100981

Cited by 4 publications

(4 citation statements)

References 199 publications

(223 reference statements)

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“…A recent threedimensional electron microscopy study revealed different mitochondrial networks, morphology and interactions with other cellular components compared to the other muscles, implying that the energy demand regulates mitochondria [152]. The decreased mitochondrial function causes cardiac dysfunction and leads to cardiomyopathy with sarcomere disarray, suggestive of mitochondrial involvement in sarcomere organization or homeostasis [153][154][155].…”

Section: (A) Mitochondriamentioning

confidence: 99%

Sarcomere maturation: function acquisition, molecular mechanism, and interplay with other organelles

Ahmed

Tokuyama

Anzai

et al. 2022

Phil. Trans. R. Soc. B

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During postnatal cardiac development, cardiomyocytes mature and turn into adult ones. Hence, all cellular properties, including morphology, structure, physiology and metabolism, are changed. One of the most important aspects is the contractile apparatus, of which the minimum unit is known as a sarcomere. Sarcomere maturation is evident by enhanced sarcomere alignment, ultrastructural organization and myofibrillar isoform switching. Any maturation process failure may result in cardiomyopathy. Sarcomere function is intricately related to other organelles, and the growing evidence suggests reciprocal regulation of sarcomere and mitochondria on their maturation. Herein, we summarize the molecular mechanism that regulates sarcomere maturation and the interplay between sarcomere and other organelles in cardiomyocyte maturation. This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.

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Section: (A) Mitochondriamentioning

confidence: 99%

Sarcomere maturation: function acquisition, molecular mechanism, and interplay with other organelles

Ahmed

Tokuyama

Anzai

et al. 2022

Phil. Trans. R. Soc. B

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“…Overall, changes in cell structure or shape, such as hypertrophy, could be a more successful target for in vitro disease models [ 61 ]. Mitochondrial hypertrophy disease models established from patient iPSC-CMs have also been recently reviewed [ 62 ].…”

Section: Induced Pluripotent Stem Cells (Ipscs)mentioning

confidence: 99%

Stem Cell Studies in Cardiovascular Biology and Medicine: A Possible Key Role of Macrophages

Kawaguchi

Nakanishi

2022

Biology

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Stem cells are used in cardiovascular biology and biomedicine, and research in this field is expanding. Two types of stem cells have been used in research: induced pluripotent and somatic stem cells. Stem cell research in cardiovascular medicine has developed rapidly following the discovery of different types of stem cells. Induced pluripotent stem cells (iPSCs) possess potent differentiation ability, unlike somatic stem cells, and have been postulated for a long time. However, differentiating into adult-type mature and functional cardiac myocytes (CMs) remains difficult. Bone marrow stem/stromal cells (BMSCs), adipose-derived stem cells (ASCs), and cardiac stem cells (CSCs) are somatic stem cells used for cardiac regeneration. Among somatic stem cells, bone marrow stem/stromal cells (BMSCs) were the first to be discovered and are relatively well-characterized. BMSCs were once thought to have differentiation ability in infarcted areas of the heart, but it has been identified that paracrine cytokines and micro-RNAs derived from BMSCs contributed to that effect. Moreover, vesicles and exosomes from these cells have similar effects and are effective in cardiac repair. The molecular signature of exosomes can also be used for diagnostics because exosomes have the characteristics of their origin cells. Cardiac stem cells (CSCs) differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells, and supply cardiomyocytes during myocardial infarction by differentiating into newly formed cardiomyocytes. Stem cell niches and inflammatory cells play important roles in stem cell regulation and the recovery of damaged tissues. In particular, chemokines can contribute to the communication between inflammatory cells and stem cells. In this review, we present the current status of this exciting and promising research field.

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“…Mitochondrial diseases (MDs) are rare, with a prevalence of 5–12/100,000 ( 1 ). They are characterized by oxidative phosphorylation (OXPHOS) dysfunction caused by nuclear and/or mitochondrial DNA (mtDNA) variations ( 2 – 4 ). Approximately 20–40% of children with MDs develop cardiac manifestations, such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmias, left ventricular non-compaction (LVNC), heart failure and sudden cardiac death ( 5 – 8 ), which are termed mitochondrial cardiomyopathy (MCM) ( 2 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…They are characterized by oxidative phosphorylation (OXPHOS) dysfunction caused by nuclear and/or mitochondrial DNA (mtDNA) variations ( 2 – 4 ). Approximately 20–40% of children with MDs develop cardiac manifestations, such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmias, left ventricular non-compaction (LVNC), heart failure and sudden cardiac death ( 5 – 8 ), which are termed mitochondrial cardiomyopathy (MCM) ( 2 , 4 ). Combined oxidative phosphorylation deficiency-31 (COXPD31) (OMIM: 617228) is an autosomal recessive mitochondrial disease caused by mutations in the MIPEP gene.…”

Section: Introductionmentioning

confidence: 99%

Case report: Rare novel MIPEP compound heterozygous variants presenting with hypertrophic cardiomyopathy, severe lactic acidosis and hypotonia in a Chinese infant

Lu¹,

Yin²,

Xu³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundMitochondrial intermediate peptidase, encoded by the MIPEP gene, is involved in the processing of precursor mitochondrial proteins related to oxidative phosphorylation. Only a few studies have shown that mutations in MIPEP can cause combined oxidative phosphorylation deficiency-31 (COXPD31), an autosomal recessive multisystem disorder associated with mitochondrial dysfunction. We report herein a rare case of an 8-month-old boy in China with hypertrophic cardiomyopathy (HCM), severe lactic acidosis, and hypotonia caused by novel MIPEP compound heterozygous variants.MethodsTrio-whole-exome sequencing and copy number variation sequencing were performed to identify mutated genetic loci. Sanger sequencing and quantitative real-time PCR were used to validate the candidate single nucleotide variants and copy number variants, respectively.ResultsThe proband was an 8-month-old boy with HCM, severe lactic acidosis, and hypotonia who died 2 months after his first admission. Two novel compound heterozygous variants, c.1081T > A (p. Tyr361Asn) and a whole deletion (Ex1-19 del), were found in the MIPEP gene, which were inherited from his healthy parents respectively. Additionally, his mitochondria DNA copy number was significantly reduced.ConclusionWe are the first to report a patient with rare MIPEP variants in China. Our findings expand the mutation spectrum of MIPEP, and provide insights into the genotype-phenotype relationship in COXPD31.

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

Cited by 4 publications

References 199 publications

Sarcomere maturation: function acquisition, molecular mechanism, and interplay with other organelles

Sarcomere maturation: function acquisition, molecular mechanism, and interplay with other organelles

Stem Cell Studies in Cardiovascular Biology and Medicine: A Possible Key Role of Macrophages

Case report: Rare novel MIPEP compound heterozygous variants presenting with hypertrophic cardiomyopathy, severe lactic acidosis and hypotonia in a Chinese infant

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