FUNDC1 collaborates with PINK1 in regulating mitochondrial Fission and compensating for PINK1 deficiency

Jing Xu; Zhouyang Deng; Shuai Shang; Caifang Wang; Hailong Han

doi:10.1016/j.bbrc.2023.149210

FUNDC1 collaborates with PINK1 in regulating mitochondrial Fission and compensating for PINK1 deficiency

Biochem Biophys Res Commun. 2023 Dec 20:687:149210. doi: 10.1016/j.bbrc.2023.149210. Epub 2023 Nov 1.

Authors

Jing Xu¹, Zhouyang Deng¹, Shuai Shang¹, Caifang Wang², Hailong Han³

Affiliations

¹ Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, 410008, China.
² Institute of Molecular Precision Medicine, Xiangya Hospital, Key Laboratory of Molecular Precision Medicine of Hunan Province, Central South University, Changsha, Hunan, 410008, China.
³ Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, 410008, China; Department of Neurosciences, University of South China Medical School, Hengyang, Hunan, 421001, China. Electronic address: hanhailong@sklmg.edu.cn.

PMID: 37931419
DOI: 10.1016/j.bbrc.2023.149210

Abstract

Parkinson's disease is presently thought to have its molecular roots in the alteration of PINK1-mediated mitophagy and mitochondrial dynamics. Finding new suppressors of the pathway is essential for developing cutting-edge treatment approaches. Our study shows that FUNDC1 suppressed PINK1 mutant phenotypes in Drosophila. The restoration of PINK1-deficient phenotypes through FUNDC1 is not reliant on its LC3-binding motif Y (18)L (21) or autophagy-related pathway. Moreover, the absence of Drp1 affects the phenotypic restoration of PINK1 mediated by FUNDC1 in flies. In summary, our findings have unveiled a fresh mechanism through which FUNDC1 compensates for the loss of PINK1, operating independently of autophagy but exerting its influence via interaction with Drp1.

Keywords: Autophagy receptor; Drp1; Mitochondrial dynamics; PD; Ubiquitin-independent mitophagy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / genetics
Drosophila / genetics
Drosophila / metabolism
Drosophila Proteins* / genetics
Mitochondrial Dynamics* / genetics
Mitophagy / genetics
Protein Kinases / genetics
Protein Kinases / metabolism
Protein Serine-Threonine Kinases / metabolism
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism

Substances

Ubiquitin-Protein Ligases
Protein Kinases
PINK1 protein, Drosophila
Protein Serine-Threonine Kinases
Drosophila Proteins