Impaired protein quality control system underlies mitochondrial dysfunction in skeletal muscle of streptozotocin-induced diabetic rats

• Type: Article in International Scientific Journal
• Date: 2012

Authors

padrao, ai (Author) Other; carvalho, t (Author) Other; vitorino, r (Author) Other; alves, rmp (Author) Other; caseiro, a (Author) Other; duarte, ja (Author) FADEUP; ferreira, r (Author) Other; amado, f (Author) Other

Journal

Title: Biochimica et Biophysica Acta - Molecular Basis of Disease

Vol. 1822

Pages: 1189-1197

ISSN: 0925-4439

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 14 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-002-7Q9

DOI: 10.1016/j.bbadis.2012.04.009

Abstract (EN): Hyperglycaemia-related mitochondrial impairment is suggested as a contributor to skeletal muscle dysfunction. Aiming a better understanding of the molecular mechanisms that underlie mitochondrial dysfunction in type 1 diabetic skeletal muscle, the role of the protein quality control system in mitochondria functionality was studied in intermyofibrillar mitochondria that were isolated from gastrocnemius muscle of streptozotocin (STZ)-induced diabetic rats. Hyperglycaemic rats showed more mitochondria but with lower ATP production ability, which was related with increased carbonylated protein levels and lower mitochondrial proteolytic activity assessed by zymography. LC-MS/MS analysis of the zymogram bands with proteolytic activity allowed the identification of an AAA protease, Lon protease; the metalloproteases PreP, LAP-3 and MIP; and cathepsin D. The content and activity of the Lon protease was lower in the STZ animals, as well as the expression of the m-AAA protease paraplegin, evaluated by western blotting. Data indicated that in muscle from diabetic rats the mitochondrial protein quality control system was compromised, which was evidenced by the decreased activity of AAA proteases, and was accompanied by the accumulation of oxidatively modified proteins, thereby causing adverse effects on mitochondrial functionality.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9