Increased longevity of some C. elegans mitochondrial mutants explained by activation of an alternative energy-producing pathway

The Caenorhabditis elegans misc-1 gene encodes a mitochondrial carrier with a role in oxidative stress response. The knock-out mutant has no lifespan phenotype and fails to upregulate the gei-7-mediated glyoxylate shunt, an extra-mitochondrial pathway of energy production. We show that gei-7 is required for the longevity of the mitochondrial mutant clk-1. Our data suggest that only mitochondrial mutants that upregulate gei-7 can achieve longevity.     

多功能蛋白p62调节细胞自噬及相关疾病的研究进展

Sequestosome 1 （p62/SQSTM1）是一种由应激诱导产生的细胞内蛋白并作用于选择性自噬的多功能蛋白.p62包含多种蛋白作用域,可结合聚泛素化蛋白并将其进一步降解,在信号转导过程中发挥重要作用.研究表明,p62参与多种疾病的病理过程,如神经退行性疾病、糖尿病、肥胖甚至是癌症.因而从p62的结构和功能这两方面阐述其在相关疾病中的作用很有必要.     

Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress

The mev-1 gene encodes cytochrome b, a large subunit of the Complex II enzyme succinate-CoQ oxidoreductase. The mev-1(kn1) mutants are hypersensitive to oxidative stress and age precociously, probably because of elevated superoxide anion production in mitochondria. Coenzyme Q (CoQ) is essential for the mitochondrial respiratory chain. Here, we show that CoQ(10) and Vitamin E extended the life span of wild-type Caenorhabditis elegans. Conversely, only CoQ(10) recovered the life shortening effects seen in mev-1. We also show that CoQ(10) but not Vitamin E reduced superoxide anion levels in wild type and mev-1. Another previously described phenotype of mev-1 animals is the presence of supernumerary apoptotic cells. We now demonstrate that CoQ(10) (but not Vitamin E) suppressed these supernumerary apoptoses. Collectively these data suggest that exogenously supplied CoQ(10) can play a significant anti-aging function. It may do so either by acting as an antioxidant to dismutate the free radical superoxide anion or by reducing the uncoupling of reactions during election transport that could otherwise result in superoxide anion production. The latter activity has not been ascribed to CoQ(10); however, it is known that conditions that uncouple electron transport reactions can lead to elevated superoxide anion production.