Fndc-1 contributes to paternal mitochondria elimination in C. elegans

Lim, Young‐Hun; Rubio-Peña, Karinna; Sobraske, Peter J.; Molina, Paola A.; Brookes, Paul S.; Galy, Vincent; Nehrke, Keith

doi:10.1016/j.ydbio.2019.06.016

Cited by 36 publications

(18 citation statements)

References 29 publications

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“…The mitochondrial cox-1 gene has been frequently used to infer evolutionary distances between species as well as between populations ( Cavallero et al, 2013 ; Amor et al, 2016 ; Springer et al, 2001 ; Wiens et al, 2010 ; Zardoya and Meyer, 1996 ; Zou et al, 2017 ) due to its rapid mutation rate, lack of recombination and relatively constant rate of change over time ( Brown et al, 1979 ; Giles et al, 1980 ; Harrison, 1989 ). Existing data suggest that mitochondria are inherited maternally in C. elegans ( Lim et al, 2019 ; Zhou et al, 2011 ; Sato and Sato, 2011 ; Wang et al, 2017 ) and Ascaris ( Anderson et al, 1995 ). Previous cox-1 phylogeny studies resolve Ascaris spp.…”

Section: Resultsmentioning

confidence: 99%

Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans

Easton

Gao

Lawton

et al. 2020

eLife

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Human ascariasis is a major neglected tropical disease caused by the nematode Ascaris lumbricoides. We report a 296 megabase (Mb) reference-quality genome comprised of 17,902 protein-coding genes derived from a single, representative Ascaris worm. An additional 68 worms were collected from 60 human hosts in Kenyan villages where pig husbandry is rare. Notably, the majority of these worms (63/68) possessed mitochondrial genomes that clustered closer to the pig parasite Ascaris suum than to A. lumbricoides. Comparative phylogenomic analyses identified over 11 million nuclear-encoded SNPs but just two distinct genetic types that had recombined across the genomes analyzed. The nuclear genomes had extensive heterozygosity, and all samples existed as genetic mosaics with either A. suum-like or A. lumbricoides-like inheritance patterns supporting a highly interbred Ascaris species genetic complex. As no barriers appear to exist for anthroponotic transmission of these ‘hybrid’ worms, a one-health approach to control the spread of human ascariasis will be necessary.

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Section: Resultsmentioning

confidence: 99%

Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans

Easton

Gao

Lawton

et al. 2020

eLife

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“…An important paralog of FUNDC2 is FUNDC1, which is highly conserved and regulates mitophagy and inflammatory response. It has been recently shown that the ortholog of FUNDC1 in Caenorhabditis elegans (no FUNDC2 in C. elegans) is strongly expressed in sperm and contributes to paternal mitochondria elimination in sperm (Lim et al, 2019). The most likely interacting protein for FUNDC2 is FUNDC1 as predicted by the STRING Interaction Network in the GeneCards database, suggesting functional conservation.…”

Section: Discussionmentioning

confidence: 99%

Deletion of FUNDC2 and CMC4 on Chromosome Xq28 Is Sufficient to Cause Hypergonadotropic Hypogonadism in Men

Deng

Pathak

et al. 2020

Front. Genet.

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Background: Hypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated. Methods: Here, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion. Results: Our patient's Xq28 deletion is 44,806 bp and contains only two genes, FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes (DEGs) in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier (SCB) regulation, apoptosis, inflammatory response, and gonadotropin-releasing regulation. Indeed, our patient has an elevated follicle stimulating hormone (FSH) level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation (XCI) is skewed toward the deleted X, suggesting a mechanism to avoid FSH dysregulation. Conclusion: Compared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and CMC4 results in dysregulation of apoptosis, inflammation, and FSH, and is sufficient to cause Xq28-associated HH.

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“…FUN14 domain containing 1 (FUNDC1) is an outer mitochondrial membrane protein with three transmembrane domains, which serves as a mitophagy receptor in mitochondrial uncoupling-, and hypoxia-mediated mitophagy as well as paternal mitochondrial clearance in C. elegans (Liu et al, 2012;Chen et al, 2014;Lim et al, 2019). FUNDC1 contains a conserved microtubule associated protein 1 light chain 3 beta (MAP1LC3B better known as LC3)-interacting region (LIR) domain facing the cytosol, which is necessary for its interaction with LC3, a key regulator of autophagy (Liu et al, 2012).…”

Section: Fundc1-mediated Mitophagymentioning

confidence: 99%

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Guo

Kroemer

2020

Front. Cell Dev. Biol.

247

159

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Mitochondrial dysfunction constitutes one of the hallmarks of aging and is characterized by irregular mitochondrial morphology, insufficient ATP production, accumulation of mitochondrial DNA (mtDNA) mutations, increased production of mitochondrial reactive oxygen species (ROS) and the consequent oxidative damage to nucleic acids, proteins and lipids. Mitophagy, a mitochondrial quality control mechanism enabling the degradation of damaged and superfluous mitochondria, prevents such detrimental effects and reinstates cellular homeostasis in response to stress. To date, there is increasing evidence that mitophagy is significantly impaired in several human pathologies including aging and age-related diseases such as neurodegenerative disorders, cardiovascular pathologies and cancer. Therapeutic interventions aiming at the induction of mitophagy may have the potency to ameliorate these dysfunctions. In this review, we summarize recent findings on mechanisms controlling mitophagy and its role in aging and the development of human pathologies.

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Fndc-1 contributes to paternal mitochondria elimination in C. elegans

Cited by 36 publications

References 29 publications

Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans

Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans

Deletion of FUNDC2 and CMC4 on Chromosome Xq28 Is Sufficient to Cause Hypergonadotropic Hypogonadism in Men

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

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