title: Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons.
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.
authors.affiliation: Institute of Molecular Medicine, National Taiwan University, 10002 Taipei, Taiwan;
authors.forename: Hao-Ching
authors.initials: HC
authors.lastname: Jiang
authors.affiliation: Institute of Molecular Medicine, National Taiwan University, 10002 Taipei, Taiwan;
authors.forename: Jiun-Min
authors.initials: JM
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Medicine, National Taiwan University, 10002 Taipei, Taiwan;
authors.forename: Chien-Ping
authors.initials: CP
authors.lastname: Yen
authors.affiliation: Department of Neurology, National Taiwan University Hospital, 10002 Taipei, Taiwan;
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chao
authors.affiliation: Institute of Molecular Medicine, National Taiwan University, 10002 Taipei, Taiwan; Institute of Biological Chemistry, Academia Sinica, 11529 Taipei, Taiwan.
authors.forename: Ruey-Hwa
authors.initials: RH
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, National Taiwan University, 10002 Taipei, Taiwan; chunliangpan@gmail.com.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Pan
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D008136:Longevity; D008928:Mitochondria / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D010084:Oxidation-Reduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: C. elegans; CaMKII; mitochondria; neural activity; neuronal aging