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Fundc1 Deficiency Exacerbates Pathological Cardiac Remodeling And Contractile Dysfunction Through Suppression Of Drp1

Circulation(2017)

Cited 23|Views6
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Abstract
Background: FUNDC1 (Fun14 domain containing protein 1) is a mitochondrial outer membrane protein to function in the recruitment of autophagic isolated membrane to mitochondria in hypoxic conditions. However, the role for FUNDC1 in heart failure remains unknown. Methods: Wild type and FUNDC1 deficient mice were subjected to transverse aortic constriction (TAC) for 1 month. Echocardiography was employed to evaluate the heart function. Lectin-FITC (WGA) and Masson Trichrome staining were used to determine cardiac remodeling. Mitophagy was measure by TEM and Pink1-Parkin and Bnip3 were measured with Western Blot. Mitochondrial membrane potential was measured using JC-1 staining. ROS production was measured with DHE and mitoSOX. DRP1 and its S616 and S637 phosphorylation were evaluated using Western Blot. H9C2 myoblasts were employed for gain and loss of function for DRP1 using siRNA and adenovirus transfection. Results: Chronic pressure overload triggered pathological cardiac remodeling (hypertrophy and inter...
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Key words
Autophagy, Cardiomyopathy, Heart failure, Mitochondria
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