Elimination of paternal mitochondria through the lysosomal degradation pathway in C. elegans

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Lysosomal degradation of paternal mitochondria 1662

Cell Research (2011) 21:1662-1669. 2011 IBCB, SIBS, CAS All rights reserved 1001-0602/11 $ 32.00

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ORIGINAL ARTICLE

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Elimination of paternal mitochondria through the lysosomal degradation pathway in C. elegans

Qinghua Zhou1, Haimin Li1, Ding Xue1

1Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA

In mammals, the inheritance of mitochondrion and its DNA (mtDNA) is strictly maternal, despite the fact that a sperm can inject up to 100 functional mitochondria into the oocyte during fertilization. The mechanisms responsible for the elimination of the paternal mitochondria remain largely unknown. We report here that this paternal mitochondrial elimination process is conserved in Caenorhabditis elegans, and that the lysosomal pathway actively participates in this process. Molecular and cell biological analyses indicate that in wild-type animals paternal mitochondria and mtDNA are destroyed within two hours after fertilization. In animals with compromised lysosomes, paternal mitochondria persist until late embryonic stages. Therefore, the lysosomal pathway plays an important role in degrading paternal mitochondria introduced into the oocyte during fertilization. Our study indicates that C. elegans is an excellent animal model for understanding and dissecting this conserved biological process critical for animal development and reproduction.

Keywords: lysosomal degradation; paternal mitochondria elimination; C. elegans; maternal inheritance; mitochondria DNA; fertilized oocyteCell Research (2011) 21:1662-1669. doi:10.1038/cr.2011.182; published online 22 November 2011

Introduction

The mitochondrion is a membrane-enclosed organ-elle that carries out oxidative phosphorylation to generate a constant supply of adenosine triphosphate (ATP) in eukaryotic cells [1]. It is also the only organelle that contains its own genome (mtDNA) in animals, which encodes multiple protein components of the oxidative phosphorylation complexes I, III, IV, and V [1, 2]. In addition to being an ATP-producing organelle, the mitochondrion also plays critical roles in regulating other cellular processes, including apoptosis [3].

It has been a paradox in development that mammals inherit their mitochondria exclusively from their female parents, despite the fact that the fertilizing spermatozoon could introduce up to 100 mitochondria into the oocyte at the moment of fertilization [4, 5]. Several different theories have been proposed to account for this observa-

tion, including dilution or active destruction of paternal mitochondria in the dividing embryo [6, 7], restricted localization of paternal mitochondria to a...