title: Regulation of mitochondrial genome inheritance by autophagy and ubiquitin-proteasome system: implications for health, fitness, and fertility.
abstract: Mitochondria, the energy-generating organelles, play a role in numerous cellular functions including adenosine triphosphate (ATP) production, cellular homeostasis, and apoptosis. Maternal inheritance of mitochondria and mitochondrial DNA (mtDNA) is universally observed in humans and most animals. In general, high levels of mitochondrial heteroplasmy might contribute to a detrimental effect on fitness and disease resistance. Therefore, a disposal of the sperm-derived mitochondria inside fertilized oocytes assures normal preimplantation embryo development. Here we summarize the current research and knowledge concerning the role of autophagic pathway and ubiquitin-proteasome-dependent proteolysis in sperm mitophagy in mammals, including humans. Current data indicate that sperm mitophagy inside the fertilized oocyte could occur along multiple degradation routes converging on autophagic clearance of paternal mitochondria. The influence of assisted reproductive therapies (ART) such as intracytoplasmic sperm injection (ICSI), mitochondrial replacement (MR), and assisted fertilization of oocytes from patients of advanced reproductive age on mitochondrial function, inheritance, and fitness and for the development and health of ART babies will be of particular interest to clinical audiences. Altogether, the study of sperm mitophagy after fertilization has implications in the timing of evolution and developmental and reproductive biology and in human health, fitness, and management of mitochondrial disease.
authors.affiliation: Division of Animal Science, and Departments of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO 65211-5300, USA.
authors.forename: Won-Hee
authors.identifier: 0000-0003-2978-2774
authors.initials: WH
authors.lastname: Song
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: John William Oman
authors.initials: JW
authors.lastname: Ballard
authors.affiliation: Division of Animal Science, and Departments of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO 65211-5300, USA ; Division of Biotechnology, College of Environmental & Bioresource Sciences, Chonbuk National University, Iksan-si, Jeonbuk 570-752, Republic of Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Yi
authors.affiliation: Division of Animal Science, and Departments of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO 65211-5300, USA.
authors.forename: Peter
authors.identifier: 0000-0002-9231-2823
authors.initials: P
authors.lastname: Sutovsky
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D054629:Genome, Mitochondrial / Q000502:physiology*; D006801:Humans; D008297:Male; D063306:Mitophagy / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D059748:Proteolysis; D013079:Sperm Maturation / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex