< i > Drosophila < /i > ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle

by Woongchang Yoon, Sun-Hong Hwang, Sang-Hee Lee, Jongkyeong Chung The function of AarF domain-containing kinase 1 (ADCK1) has not been thoroughly revealed. Here we identified that ADCK1 utilizes YME1-like 1 ATPase (YME1L1) to control optic atrophy 1 (OPA1) and inner membrane mitochondrial protein (IMMT) in regulating mitochondrial dynamics and cristae structure. We firstly observed that a serious developmental impairment occurred inDrosophila ADCK1 (dADCK1) deletion mutant, resulting in premature death before adulthood. By using temperature sensitive ubiquitously expression drivertub-Gal80ts/tub-Gal4 or muscle-specific expression drivermhc-Gal4, we observed severely defective locomotive activities and structural abnormality in the muscle along with increased mitochondrial fusion in thedADCK1 knockdown flies. Moreover, decreased mitochondrial membrane potential, ATP production and survival rate along with increased ROS and apoptosis in the flies further demonstrated that the structural abnormalities of mitochondria induced bydADCK1 knockdown led to their functional abnormalities. Consistent with the ADCK1 loss-of-function data inDrosophila, ADCK1 over-expression induced mitochondrial fission and clustering in addition to destruction of the cristae structure inDrosophila and mammalian cells. Interestingly, knockdown ofYME1L1 rescued the phenotypes of ADCK1 over-expression. Furthermore, genetic epistasis from fly genetics and mammalian cell biology experiments led us to discov...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research