Striated preferentially expressed gene deficiency leads to mitochondrial dysfunction in developing cardiomyocytes

AbstractA deficiency of striated  preferentially expressed gene (Speg), a member of the myosin light chain kinase family, results in abnormal myofibril structure and function of immature cardiomyocytes (CMs), corresponding with a dilated cardiomyopathy, heart failure and perinatal death. Mitochondrial development plays a role in cardiomyocyte maturation. Therefore, this study investigated whetherSpeg deficiency ( – / – ) in CMs would result in mitochondrial abnormalities.Speg wild-type andSpeg−/− C57BL/6 littermate mice were utilized for assessment of mitochondrial structure by transmission electron and confocal microscopies. Speg was expressed in the first and second heart fields at embryonic (E) day 7.5, prior to the expression of mitochondrial Na+/Ca2+/Li+ exchanger (NCLX) at E8.5. Decreases in NCLX expression (E11.5) and the mitochondrial-to-nuclear DNA ratio (E13.5) were observed inSpeg−/− hearts. Imaging of E18.5Speg−/− hearts revealed abnormal mitochondrial cristae, corresponding with decreased ATP production in cells fed glucose or palmitate, increased levels of mitochondrial superoxide and depolarization of mitochondrial membrane potential. Interestingly, phosphorylated (p) PGC-1 α, a key mediator of mitochondrial development, was significantly reduced inSpeg−/− hearts during screening for targeted genes. Besides Z-line expression, Speg partially co-localized with PGC-1 α in the sarcomeric region and was found in the same complex by co-immunopr...
Source: Basic Research in Cardiology - Category: Cardiology Source Type: research