Defects in Mitochondrial Biogenesis Drive Mitochondrial Alterations in PARKIN-Deficient Human Dopamine Neurons

• DOI: 10.1016/j.stemcr.2020.07.013
• Publication Date: 2020-08-13T14:54:28Z
• Authors: Manoj Kumar; Jesús Acevedo-Cin...; Aanishaa Jhaldiyal; Hu Wang; Shaida A. Andrabi; Stephen Eacker; Senthilkumar S. K...; Saurav Brahmachari; Rong Chen; Hyesoo Kim; Han Seok Ko; Valina L. Dawson; Ted M. Dawson
• Keywords: PINK1

Mutations and loss of activity in PARKIN, an E3 ubiquitin ligase, play a role the pathogenesis Parkinson's disease (PD). PARKIN regulates many aspects mitochondrial quality control including autophagy (mitophagy) biogenesis. Defects mitophagy have been hypothesized to predominant dopamine (DA) neurons PD. Here, we show that although there are defects human DA lacking deficits primarily due biogenesis driven by upregulation PARIS subsequent downregulation PGC-1α. CRISPR/Cas9 knockdown completely restores function without affecting mitophagy. These results highlight importance versus PD inactivation or neurons.