Premium
Cardiac myocyte‐specific deletion of Heat shock protein 10 results in altered cytosolic and mitochondrial protein expression (699.6)
Author(s) -
Suarez Jorge,
Wang Hong,
Ouyang Kunfu,
Scott Brian
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.699.6
Subject(s) - heat shock protein , hsp60 , biology , proteolysis , mitochondrion , microbiology and biotechnology , proteostasis , hsp70 , gene , biochemistry , enzyme
Heat shock proteins (HSPs) are molecular chaperones that prevent protein damage and proteolysis. HSP10 forms mitochondrial (Mito) chaperoning complexes with HSP60 to maintain protein quality control. Studies in vitro suggest that HSP10 plays a role in normal Mito function; however, its physiological function in the heart in vivo remains to be determined. To investigate the function of cardiac HSP10, we generated a floxed allele of the Hspe1 gene, and found that cardiac specific, tamoxifen‐inducible deletion of HSP10 in adult mice resulted in death between 12 and 18 weeks after HSP10 deletion. Increased mortality after HSP10 deletion was associated with dramatically altered protein expression patterns. For instance, cardiac hypertrophic biomarkers atrial natriuretic factor (ANF), β‐Myosin Heavy Chain (βMHC) and skeletal muscle actin were increased in the HSP10 KO mice. In Addition, there was a dramatic reduction in levels of Mito respiratory complex subunits including CI‐NDUFA9, CII‐30, COX I, COX IV, and COX Vb. Furthermore, the apoptotic pathway is activated in HSP10 KO mice as revealed by the cleavage of Caspases 9 and 3. Our results suggest that mitochondrial protein damage may be the primary pathological cause of the death. In conclusion, HSP10 plays a critical and vital role in regulating mitochondrial protein homeostasis. Grant Funding Source : Supported by P. Robert Majumder Charitable Foundation.