Autophagy and proteotoxicity in cardiomyocytes

 Abstract

Increasing evidence suggests that misfolded proteins and intracellular aggregates contribute to cardiac disease and heart failure. We wished to determine if autophagic induction by Atg7 is sufficient to reduce misfolded protein and aggregate content in protein misfolding-stressed cardiomyocytes. We used loss- and gain-of-function approaches in cultured cardiomyocytes to determine the effects of ATG7 knockdown and Atg7 overexpression in protein conformation-based toxicity induced by expression of a mutant aB crystallin (CryABR120G) known to cause human heart disease. We show that Atg7 induces basal autophagy and rescues the CryAB accumulation of misfolded proteins and aggregates in cardiomyocytes.

 Related Article:

G Seebohm, N Strutz-Seebohm, ON Ureche, U Henrion, R Baltaev, AF Mack, G Korniychuk, K Steinke, D Tapken, A Pfeufer, S Kääb, C Bucci, B Attali, J Merot, JM Tavare, UC Hoppe, MC Sanguinetti, F Lang. Long QT syndrome-associated mutations in KCNQ1 and KCNE1 subunits disrupt normal endosomal recycling of IKs channels. Circ Res 2008; 103: 1451- 7.
PMID: 21493898 DOI: 10.1161/CIRCRESAHA.1

Full Text Options
Article
Metrics
 Share
 Full Text
 Info
Pages
1259 - 1260
doi
10.4161/auto.7.10.16882
Type
Autophagic Punctum
 Metrics
 Cite This Article
 Permissions
 Permissions
 Reprints
Autophagy and proteotoxicity in cardiomyocytes