Inhibition of bioenergetics provides novel insights into recruitment of PINK1-dependent neuronal mitophagy
Yea Seul Shin, James G Ryall, Joanne M Britto, Chew L Lau, Rodney J Devenish, Phillip Nagley, Philip M Beart
JOURNAL OF NEUROCHEMISTRY | WILEY | Published : 2019
Contributions of damaged mitochondria to neuropathologies have stimulated interest in mitophagy. We investigated triggers of neuronal mitophagy by disruption of mitochondrial energy metabolism in primary neurons. Mitophagy was examined in cultured murine cerebellar granule cells after inhibition of mitochondrial respiratory chain by drugs rotenone, 3-nitropropionic acid, antimycin A, and potassium cyanide, targeting complexes I, II, III, and IV, respectively. Inhibitor concentrations producing slow cellular demise were determined from analyses of cellular viability, morphology of neuritic damage, plasma membrane permeability, and oxidative phosphorylation. Live cell imaging of dissipation of..View full abstract
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Awarded by National Health and Medical Research Council (Australia)
The authors declare no conflict of interest. YSS was in receipt of a scholarship from Australian Postgraduate Award and the University of Melbourne. This work was supported by the National Health and Medical Research Council (Australia) (APP509217), of which PMB was a Research Fellow (APP1020401). PN and RJD were supported by the Australian Research Council. PMB acknowledges support of Operational Infrastructure Scheme from the Victorian Government Department of Business and Innovation. We thank Dr Carlos Rosado and Dr Percy Chu for advice and assistance in this work. The generous provision of the PINK1 antibody by Dr Janetta Culvenor is gratefully acknowledged.