title: PINK1 is required for timely cell-type specific mitochondrial clearance during Drosophila midgut metamorphosis.
abstract: Mitophagy is the selective degradation of mitochondria by autophagy, which is an important mitochondrial quality and quantity control process. During Drosophila metamorphosis, the degradation of midgut involves a large change in length and organization, which is mediated by autophagy. Here we noticed a cell-type specific mitochondrial clearance process that occurs in enterocytes (ECs), while most mitochondria remain in intestinal stem cells (ISCs) during metamorphosis. Although PINK1/PARKIN represent the canonical pathway for the elimination of impaired mitochondria in varied pathological conditions, their roles in developmental processes or normal physiological conditions have been less studied. To examine the potential contribution of PINK1 in developmental processes, we monitored the dynamic expression pattern of PINK1 in the midgut development by taking advantage of a newly CRISPR/Cas9 generated knock-in fly strain expressing PINK1-mCherry fusion protein that presumably recapitulates the endogenous expression pattern of PINK1. We disclosed a spatiotemporal correlation between the expression pattern of PINK1 and the mitochondrial clearance or persistence in ECs or ISCs respectively. By mosaic genetic analysis, we then demonstrated that PINK1 and PARKIN function epistatically to mediate the specific timely removal of mitochondria, and are involved in global autophagy in ECs during Drosophila midgut metamorphosis, with kinase-dead PINK1 exerting dominant negative effects. Taken together, our studies concluded that the PINK1/PARKIN is crucial for timely cell-type specific mitophagy under physiological conditions and demonstrated again that Drosophila midgut metamorphosis might serve as an elegant in vivo model to study autophagy.
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China.
authors: Yan
authors: Y
authors: Liu
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China.
authors: Jingjing
authors: J
authors: Lin
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China.
authors: Minjie
authors: M
authors: Zhang
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China.
authors: Kai
authors: K
authors: Chen
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China.
authors: Shengxi
authors: S
authors: Yang
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China.
authors: Qun
authors: Q
authors: Wang
authors: Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China.
authors: Hongqin
authors: H
authors: Yang
authors: Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China.
authors: Shusen
authors: S
authors: Xie
authors: Department of Gastric Surgery, Union Hospital of Fujian Medical University, Fujian 350001, China.
authors: Yongjian
authors: Y
authors: Zhou
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China.
authors: Xi
authors: X
authors: Zhang
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China. Electronic address: sandyfeichen@fzu.edu.cn.
authors: Fei
authors: F
authors: Chen
authors: Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian Province 350108, China; Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China. Electronic address: yangyf@fzu.edu.cn.
authors: Yufeng
authors: Y
authors: Yang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D020895:Enterocytes / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D007422:Intestines / Q000196:embryology* / Q000648:ultrastructure; D007814:Larva; D008675:Metamorphosis, Biological; D008928:Mitochondria / Q000378:metabolism; D063306:Mitophagy / Q000502:physiology*; D009024:Morphogenesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011679:Pupa; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology; D000099202:PTEN-Induced Putative Kinase
chemical_list: D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D044767:Ubiquitin-Protein Ligases; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase; C487430:park protein, Drosophila