Plucinska, G., Paquet, D., Hruscha, A., Godinho, L., Haass, C., Schmid, B., and Misgeld, T. (2012) In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system. The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(46):16203-16212.
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.