Mitochondrial Inheritance Following Nuclear Transfer: From Cloned Animals to Patients with Mitochondrial Disease

Burgstaller, Joerg P.; Chiaratti, Marcos Roberto

doi:10.1007/978-1-0716-3064-8_4

Cited by 3 publications

(1 citation statement)

References 196 publications

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“…Furthermore, the novel reproductive technologies known as mitochondrial donation or mitochondrial replacement therapy (MRT), raise challenging ethical and safety issues, as only a few successful MRT case reports are available. Furthermore, since we still lack long-term studies of MRT outcomes, the potential risks of both major mtDNA heteroplasmy and the mixing of genetic materials (nuclear and mitochondrial genomes) from three parents are under much debate [103][104][105][106][107] . Therefore, delineating the molecular pathway underlying PME and the (possible negative) effects of PM persistence on the developing embryo, will allow for deeper understanding of the importance of this highly conserved phenomenon for embryo development, and may ultimately lead to the development and/or modification of MAR technologies that guard against these effects.…”

Section: Discussionmentioning

confidence: 99%

Egg MVBs elicit an antimicrobial pathway to degrade paternal mitochondria after fertilization

Ben-Hur,

Afar,

Politi

et al. 2023

Preprint

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Mitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination (PME) after fertilization are far less clear. UsingDrosophila, we show that special egg-derived multivesicular bodies (MVBs) promote PME by activating LC3-associated phagocytosis (LAP), a cellular defense pathway commonly employed against invading microbes. Upon fertilization, the egg MVBs engage and densely coat the sperm flagellum, forming extended flagellum vesicular sheaths (FVSs), within which the paternal mitochondria degrade. Inactivation of multiple LAP pathway components, such as Rubicon, a LAP-specific class III PI(3)K complex protein, significantly attenuates PME. Furthermore, recruitment of Atg8/LC3 to the FVS requires both Rubicon and the Atg8/LC3 conjugation machinery. Other LAP pathway events, such as production of the phospholipid PtdIns(3)P and reactive oxygen species (ROS), also unfold during PME. Finally, we provide evidence that a similar pathway might also mediate PME in mammals, highlighting the notion that eggs may regard paternal mitochondria as potentially dangerous trespassers.

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Section: Discussionmentioning

confidence: 99%

Egg MVBs elicit an antimicrobial pathway to degrade paternal mitochondria after fertilization

Ben-Hur,

Afar,

Politi

et al. 2023

Preprint

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Enhancing the quality of inferior oocytes of buffalo for in vitro embryo production: The impact of melatonin on maturation, SCNT, and epigenetic modifications

Kumari,

Saini,

Thakur

et al. 2024

Tissue and Cell

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Egg multivesicular bodies elicit an LC3-associated phagocytosis-like pathway to degrade paternal mitochondria after fertilization

Ben-Hur,

Sernik,

Afar

et al. 2024

Nat Commun

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Mitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination after fertilization are far less clear. Using Drosophila, we show that special egg-derived multivesicular body vesicles promote paternal mitochondrial elimination by activating an LC3-associated phagocytosis-like pathway, a cellular defense pathway commonly employed against invading microbes. Upon fertilization, these egg-derived vesicles form extended vesicular sheaths around the sperm flagellum, promoting degradation of the sperm mitochondrial derivative and plasma membrane. LC3-associated phagocytosis cascade of events, including recruitment of a Rubicon-based class III PI(3)K complex to the flagellum vesicular sheaths, its activation, and consequent recruitment of Atg8/LC3, are all required for paternal mitochondrial elimination. Finally, lysosomes fuse with strings of large vesicles derived from the flagellum vesicular sheaths and contain degrading fragments of the paternal mitochondrial derivative. Given reports showing that in some mammals, the paternal mitochondria are also decorated with Atg8/LC3 and surrounded by multivesicular bodies upon fertilization, our findings suggest that a similar pathway also mediates paternal mitochondrial elimination in other flagellated sperm-producing organisms.

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Mitochondrial Inheritance Following Nuclear Transfer: From Cloned Animals to Patients with Mitochondrial Disease

Cited by 3 publications

References 196 publications

Egg MVBs elicit an antimicrobial pathway to degrade paternal mitochondria after fertilization

Egg MVBs elicit an antimicrobial pathway to degrade paternal mitochondria after fertilization

Enhancing the quality of inferior oocytes of buffalo for in vitro embryo production: The impact of melatonin on maturation, SCNT, and epigenetic modifications

Egg multivesicular bodies elicit an LC3-associated phagocytosis-like pathway to degrade paternal mitochondria after fertilization

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