RT Journal Article SR Electronic T1 In Vivo Imaging of Disease-Related Mitochondrial Dynamics in a Vertebrate Model System JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 16203 OP 16212 DO 10.1523/JNEUROSCI.1327-12.2012 VO 32 IS 46 A1 Plucińska, Gabriela A1 Paquet, Dominik A1 Hruscha, Alexander A1 Godinho, Leanne A1 Haass, Christian A1 Schmid, Bettina A1 Misgeld, Thomas YR 2012 UL http://www.jneurosci.org/content/32/46/16203.abstract AB 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.