RRC ID 45580
著者 Kaufman DM, Crowder CM.
タイトル Mitochondrial Proteostatic Collapse Leads to Hypoxic Injury.
ジャーナル Curr Biol
Abstract Hypoxic injury is a key pathological event in a variety of diseases. Despite the clinical importance of hypoxia, modulation of hypoxic injury mechanisms for therapeutic benefit has not been achieved, suggesting that critical features of hypoxic injury have not been identified or fully understood. Because mitochondria are the main respiratory organelles of the cell, they have been the focus of much research into hypoxic injury. Previous research has focused on mitochondria as effectors of hypoxic injury, primarily in the context of apoptosis activation and calcium regulation; however, little is known about how mitochondria themselves are injured by hypoxia. Maintenance of protein folding is essential for normal mitochondrial function, whereas failure to maintain protein homeostasis (proteostasis) appears to be a component of aging and a variety of diseases. Previously, it has been demonstrated that mitochondria possess their own unfolded protein response that is activated in response to mitochondrial protein folding stress, a response that is best understood in C. elegans. Because hypoxia has been shown to disrupt ATP production and translation of nuclear encoded proteins--both of which are shown to disrupt mitochondrial proteostasis in other contexts-we hypothesized that failure to maintain mitochondrial proteostasis may play a role in hypoxic injury. Utilizing C. elegans models of global, focal, and cell non-autonomous hypoxic injury, we have found evidence of mitochondrial protein misfolding post-hypoxia and have found that manipulation of the mitochondrial protein folding environment is an effective hypoxia protective strategy.
巻・号 25(16)
ページ 2171-6
公開日 2015-8-17
DOI 10.1016/j.cub.2015.06.062
PII S0960-9822(15)00789-7
PMID 26234215
PMC PMC4938157
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / physiology* Disease Models, Animal Humans Hypoxia / physiopathology* Microscopy, Confocal Microscopy, Electron Mitochondria / metabolism* Mitochondria / ultrastructure Protein Folding* Unfolded Protein Response*
IF 9.601
引用数 15
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm4919 tm4525 tm843