biostudies-literatureAngelin AAmerican Heart AssociationNIA NIH HHSNIDDK NIH HHSNHLBI NIH HHSU.S. Department of DefenseU.S. Department of Defense (United States Department of Defense)NCI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)U.S. Department of Health & Human Services | National Institutes of HealthAmerican Heart Association (American Heart Association, Inc.)447https://www.ebi.ac.uk/biostudies/studies/S-EPMC12800341biostudies-literatureUnknown17(1)Primary mitochondrial disease (PMD) patients manifesting cardiomyopathy are twice as likely to die as other PMD patients. One PMD with cardiomyopathy is caused by null mutations in the heart-muscle isoform of the adenine nucleotide translocator (SLC25A4, ANT1) gene, with the severity of cardiomyopathy mediated by mitochondrial DNA. To optimize strategies for addressing mitochondrial cardiomyopathy, we generated an Ant1 null mouse and combined it with the ND6^P25L mitochondrial DNA mutation to mimic the hypertrophic versus dilated cardiomyopathies observed in patients. Here, we transduce the neonatal Ant1^-/- and Ant1^-/-+ND6^P25L mouse hearts with an AAV2/9-pDes-Gfp-mAnt1 cDNA vector. We show that restoration of just 10% of Ant1 gene expression was sNature communicationsPartial restoration of mitochondrial dysfunction by AAV-Ant1 protects from dilated cardiomyopathy in Ant1<sup>-/-</sup> plus mtDNA mutant mice.PMC12800341U01 HL166058R01 AG078814R01CA259635W81XWH22-1-0561W81XWH22-1-0058R01 CA259635227477R01AG078814R01DK111495W81XWH22-1-0560U01HL166058U54 HL165442R01 DK111495U54HL16544223DIVSUP1069865Carosi VWidjaja GAJanssen KOlali AAngelin AMurdock DGKeller KSule RPotluri PWallace DCBeauplan MPei LCen ZGuarnieri JWLu PfalsePartial restoration of mitochondrial dysfunction by AAV-Ant1 protects from dilated cardiomyopathy in Ant1<sup>-/-</sup> plus mtDNA mutant mice.Primary mitochondrial disease (PMD) patients manifesting cardiomyopathy are twice as likely to die as other PMD patients. One PMD with cardiomyopathy is caused by null mutations in the heart-muscle isoform of the adenine nucleotide translocator (SLC25A4, ANT1) gene, with the severity of cardiomyopathy mediated by mitochondrial DNA. To optimize strategies for addressing mitochondrial cardiomyopathy, we generated an Ant1 null mouse and combined it with the ND6^P25L mitochondrial DNA mutation to mimic the hypertrophic versus dilated cardiomyopathies observed in patients. Here, we transduce the neonatal Ant1^-/- and Ant1^-/-+ND6^P25L mouse hearts with an AAV2/9-pDes-Gfp-mAnt1 cDNA vector. We show that restoration of just 10% of Ant1 gene expression was s2025-01-01T00:00:00Z2025 Dec2026-06-06T14:58:12.206Z2026-06-01T03:08:05.22ZS-EPMC128003414139815810.1038/s41467-025-67134-4