title: Motility of astrocytic mitochondria is arrested by Ca2+-dependent interaction between mitochondria and actin filaments.
abstract: Motility of mitochondria, as well as their activity-dependent immobilization ("trapping"), is essential for neuronal function, but its regulation by cytoskeleton and relevance for glial cell signalling are unknown. Using time-lapse fluorescence imaging in rat cultured astrocytes, we evaluated the role of microtubules and actin filaments in motility of mitochondria in resting cells and during physiological or pathological Ca(2+) elevations. We found that mitochondria were significantly more aligned with microtubules than with actin filaments. Mitochondria were highly mobile under resting conditions at low intracellular free Ca(2+) concentrations ([Ca(2+)](i)). Activation of a moderate increase in [Ca(2+)](i) by either low-dose ionomycin or ATP immobilized mitochondria significantly but reversibly, without affecting mitochondrial morphology. A larger dose of ionomycin caused irreversible arrest and fragmentation of mitochondria. Disruption of microtubules completely arrested mitochondrial motility, while disruption of actin filaments had no effect on the basal mitochondrial motility at resting [Ca(2+)](i) levels but significantly reduced mitochondrial immobilization during [Ca(2+)](i) elevations. These results suggest that: (i) motility of astrocytic mitochondria is inversely related to [Ca(2+)](i), (ii) mitochondria require intact microtubules for their motility, and (iii) elevated [Ca(2+)](i) immobilizes mitochondria by strengthening their interaction with actin filaments.
authors.affiliation: Neuroscience Center, University of Helsinki, P.O. Box 56 (Viikinkaari 4), FI-00014 Helsinki, Finland.
authors.forename: Elena
authors.initials: E
authors.lastname: Kremneva
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kislin
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Kang
authors.forename: Leonard
authors.initials: L
authors.lastname: Khiroug
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015759:Ionomycin / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D059008:Time-Lapse Imaging
chemical_list: D015759:Ionomycin; D000255:Adenosine Triphosphate; D002118:Calcium