Kinetics and specificity of paternal mitochondrial elimination in Caenorhabditis elegans.

Yang Wang,Long Miao,Yi Zhang,Lianwan Chen,Byung-Ho Kang,Xiao-Ming Yin,Qian Liang,Ding Xue

doi:10.1038/ncomms12569

Abstract

In most eukaryotes, mitochondria are inherited maternally. The autophagy process is critical for paternal mitochondrial elimination (PME) in Caenorhabditis elegans, but how paternal mitochondria, but not maternal mitochondria, are selectively targeted for degradation is poorly understood. Here we report that mitochondrial dynamics have a profound effect on PME. A defect in fission of paternal mitochondria delays PME, whereas a defect in fusion of paternal mitochondria accelerates PME. Surprisingly, a defect in maternal mitochondrial fusion delays PME, which is reversed by a fission defect in maternal mitochondria or by increasing maternal mitochondrial membrane potential using oligomycin. Electron microscopy and tomography analyses reveal that a proportion of maternal mitochondria are compromised when they fail to fuse normally, leading to their competition for the autophagy machinery with damaged paternal mitochondria and delayed PME. Our study indicates that mitochondrial dynamics play a critical role in regulating both the kinetics and the specificity of PME.

Highlights

IntroductionMitochondria are inherited maternally. The autophagy process is critical for paternal mitochondrial elimination (PME) in Caenorhabditis elegans, but how paternal mitochondria, but not maternal mitochondria, are selectively targeted for degradation is poorly understood
In most eukaryotes, mitochondria are inherited maternally
In drp-1(tm1108) embryos that are defective in mitochondrial fission, long and highly connected mitochondria are observed, which often exist as asymmetric, concentrated clusters in the blastomeres (Supplementary Fig. 1b)

Summary

Introduction

Mitochondria are inherited maternally. The autophagy process is critical for paternal mitochondrial elimination (PME) in Caenorhabditis elegans, but how paternal mitochondria, but not maternal mitochondria, are selectively targeted for degradation is poorly understood. A major cellular degradation process that proceeds through formation of autophagosomes with double-layer membranes enclosing damaged or unnecessary organelles[12,13], is partially responsible for paternal mitochondrial elimination (PME), leading to their eventual degradation through lysosomes It has been enigmatic how the autophagy machinery in the embryo can selectively target paternal mitochondria, but not maternal mitochondria, for degradation. During nutrient starvation, normal cells with elongated mitochondria are protected from autophagy elimination, while fusion-deficient cells, in which mitochondria become fragmented, do not survive[22,23] These observations suggest that mitochondrial dynamics play an important role in regulating appropriate mitophagy and the functions and survival of cells. Our study provides critical insights into the long-standing, fundamental question of how paternal mitochondria are distinguished from maternal mitochondria during the PME process

Methods

Results

Conclusion