RRC ID 34752
著者 Jiang HC, Hsu JM, Yen CP, Chao CC, Chen RH, Pan CL.
タイトル Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons.
ジャーナル Proc Natl Acad Sci U S A
Abstract Decline in mitochondrial morphology and function is a hallmark of neuronal aging. Here we report that progressive mitochondrial fragmentation is a common manifestation of aging Caenorhabditis elegans neurons and body wall muscles. We show that sensory-evoked activity was essential for maintaining neuronal mitochondrial morphology, and this activity-dependent mechanism required the Degenerin/ENaC sodium channel MEC-4, the L-type voltage-gated calcium channel EGL-19, and the Ca/calmodulin-dependent kinase II (CaMKII) UNC-43. Importantly, UNC-43 phosphorylated and inhibited the dynamin-related protein (DRP)-1, which was responsible for excessive mitochondrial fragmentation in neurons that lacked sensory-evoked activity. Moreover, enhanced activity in the aged neurons ameliorated mitochondrial fragmentation. These findings provide a detailed description of mitochondrial behavior in aging neurons and identify activity-dependent DRP-1 phosphorylation by CaMKII as a key mechanism in neuronal mitochondrial maintenance.
巻・号 112(28)
ページ 8768-73
公開日 2015-7-14
DOI 10.1073/pnas.1501831112
PII 1501831112
PMID 26124107
PMC PMC4507213
MeSH Aging Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / physiology Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism* Longevity Mitochondria / physiology* Neurons / enzymology Neurons / physiology* Oxidation-Reduction
IF 9.412
引用数 20
WOS 分野 MULTIDISCIPLINARY SCIENCES
リソース情報
線虫 fzo-1(tm1133) drp-1(tm1108)