Disturbed mitochondrial maturation in cardiolipin remodeling-deficient cardiomyocytes
Year: 2026
Type: article
Abstract: Barth syndrome, a rare X-linked genetic disorder, features early-onset cardiomyopathy. The causal gene, TAFAZZIN , encodes a transacylase that mediates the acyl chain remodeling of cardiolipin, a critical phospholipid in the inner mitochondrial membrane. While Barth syndrome exhibits hallmark cardiolipin abnormalities, the precise mechanisms linking TAFAZZIN deficiency and disturbed cardiolipin metabolism to progressive cardiac dysfunction remain unclear. In this study, we modeled Barth syndrome cardiomyopathy in human induced pluripotent stem cell-derived cardiomyocytes with in vitro maturation treatments that simulate heart developmental stimuli. We found that cardiomyocyte maturation involves progressive cristae dynamics associated with protein and lipid alterations in the inner mitochondrial membrane. TAFAZZIN-deficient cardiomyocytes fail to adapt to the developmental stimuli, resulting in damaged cristae, compromised mitochondrial respiration, and cardiomyocyte dysfunction. These results demonstrate that TAFAZZIN deficiency perturbs functional and structural development of mitochondria, which may contribute to mitochondrial dysfunction and associated childhood progression to cardiomyopathy in Barth syndrome.
Source: iScience
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
Awards: G1583775748, Lipid peroxidation as driver of cardiolipin remodeling, Regulation of phospholipid remodeling in mitochondria, Role of cardiolipin in cardiac ADP/ATP translocator activity, Molecular basis to regulate the cardiac-specific form of mitochondrial phospholipid cardiolipin, G7977933134, Damage & repair of membrane lipids in health and diseases, G8703371010, G8921003365, An intimate and multifaceted partnership: cardiolipin and the mitochondrial ADP/ATP carrier
OpenAlex ID: W7130659366