title: In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system.
abstract: Mitochondria provide ATP, maintain calcium homeostasis, and regulate apoptosis. Neurons, due to their size and complex geometry, are particularly dependent on the proper functioning and distribution of mitochondria. Thus disruptions of these organelles and their transport play a central role in a broad range of neurodegenerative diseases. While in vitro studies have greatly expanded our knowledge of mitochondrial dynamics, our understanding in vivo remains limited. To address this shortcoming, we developed tools to study mitochondrial dynamics in vivo in optically accessible zebrafish. We demonstrate here that our newly generated tools, including transgenic "MitoFish," can be used to study the in vivo "life cycle" of mitochondria and allows identifying pharmacological and genetic modulators of mitochondrial dynamics. Furthermore we observed profound mitochondrial transport deficits in real time in a zebrafish tauopathy model. By rescuing this phenotype using MARK2 (microtubule-affinity regulating kinase 2), we provide direct in vivo evidence that this kinase regulates axonal transport in a Tau-dependent manner. Thus, our approach allows detailed studies of the dynamics of mitochondria in their natural environment under normal and disease conditions.
authors.affiliation: Munich Cluster for Systems Neurology, 80802 Munich, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Plucińska
authors.forename: Dominik
authors.initials: D
authors.lastname: Paquet
authors.forename: Alexander
authors.initials: A
authors.lastname: Hruscha
authors.forename: Leanne
authors.initials: L
authors.lastname: Godinho
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Bettina
authors.initials: B
authors.lastname: Schmid
authors.forename: Thomas
authors.initials: T
authors.lastname: Misgeld
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000970:Antineoplastic Agents / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D007091:Image Processing, Computer-Assisted; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D009422:Nervous System Diseases / Q000473:pathology*; D015739:Nocodazole / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011984:Sensory Receptor Cells / Q000502:physiology / Q000648:ultrastructure; D015027:Zebrafish / Q000502:physiology*; D016875:tau Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D016875:tau Proteins; D015739:Nocodazole