ATPase Inhibitory Factor-1 Disrupts Mitochondrial Ca2+ Handling and Promotes Pathological Cardiac Hypertrophy through CaMKIIδ
نویسندگان
چکیده
ATPase inhibitory factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function IF1 normal respiring is unresolved. We tested hypothesis that promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in context heart failure (HF). Methods results: Cardiac expression was increased mice humans with HF, downstream neurohumoral signaling pathways patterns resembled fetal-like gene program. Adenoviral wild-type primary cardiomyocytes resulted metabolic remodeling as evidenced by enhanced oxidative stress, reduced capacity, augmentation extramitochondrial glycolysis. Similar perturbations were observed an mutant incapable binding to synthase (E55A mutation), indication these effects occurred independent synthase. Instead, promoted fragmentation compromised Ca2+ handling, which sarcoplasmic reticulum overloading. The on handling associated cytosolic activation calcium–calmodulin kinase II (CaMKII) inhibition CaMKII or co-expression catalytically dead CaMKIIδC sufficient prevent induced hypertrophy. Conclusions: represents a novel member program contributes cardiac HF. Furthermore, we present evidence for novel, ATP-synthase-independent, role mitochondrial-to-nuclear crosstalk involving CaMKII.
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ژورنال
عنوان ژورنال: International Journal of Molecular Sciences
سال: 2021
ISSN: ['1661-6596', '1422-0067']
DOI: https://doi.org/10.3390/ijms22094427