The Enzymatic Core of the Parkinson's Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast.

ABSTRACT: Mitochondrial dysfunction is a prominent trait of cellular decline during aging and intimately linked to neuronal degeneration during Parkinson's disease (PD). Various proteins associated with PD have been shown to differentially impact mitochondrial dynamics, quality control and function, including the leucine-rich repeat kinase 2 (LRRK2). Here, we demonstrate that high levels of the enzymatic core of human LRRK2, harboring GTPase as well as kinase activity, decreases mitochondrial mass via an impairment of mitochondrial biogenesis in aging yeast. We link mitochondrial depletion to a global downregulation of mitochondria-related gene transcripts and show that this catalytic core of LRRK2 localizes to mitochondria and selectively compromises respiratory chain complex IV formation. With pro

SUBMITTER: Aufschnaiter A 

PROVIDER: S-EPMC6021522 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature