Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage in<i>C. elegans</i>

Yen, Chia‐An; Ruter, Dana L.; Turner, Christian D.; Pang, Shijin; Curran, Sean P.

doi:10.1101/456863

Cited by 10 publications

(26 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To become motile, spermatids must become activated, a sophisticated process under the control of genetic and environmental factors (Smith, 2014;Ward et al, 1983;Yen et al, 2020). In the laboratory, isolated spermatids can be activated in vitro by exposure to Pronase (Ward et al, 1983;Yen et al, 2020). We found that mafr-1 (KO) male sperm are less capable of activation upon treatment with Pronase ( Fig.…”

Section: Mafr-1 Regulates Male Sperm Fitnessmentioning

confidence: 84%

“…In addition to size, the speed of male sperm is greater than hermaphrodite-derived sperm, which also enhances male competitive advantage for fertilizing an oocyte (LaMunyon and Ward). To become motile, spermatids must become activated, a sophisticated process under the control of genetic and environmental factors (Smith, 2014;Ward et al, 1983;Yen et al, 2020). In the laboratory, isolated spermatids can be activated in vitro by exposure to Pronase (Ward et al, 1983;Yen et al, 2020).…”

Section: Mafr-1 Regulates Male Sperm Fitnessmentioning

confidence: 99%

“…In order to test the physiological consequence of mafr-1 (KO) on sperm fitness phenotypes, we designed an assay to assess sperm quality (Yen et al, 2020). When hermaphrodites are mated to WT males, nearly all resulting progeny are derived from male sperm (LaMunyon and Ward, 1995).…”

Section: Mafr-1 Regulates Male Sperm Fitnessmentioning

confidence: 99%

“…Five virgin day 1 adult males were dissected in SM buffer containing dextrose (Yen et al, 2020) to release spermatids. Spermatids were imaged using Zeiss Axio Imager, and size measured using ImageJ software.…”

Section: Sperm Size Analysismentioning

confidence: 99%

“…Five males were dissected in SM buffer containing BSA (Yen et al, 2020). An equal volume of SM buffer containing 400 μg/ml Pronase (Millipore Sigma) was added, and spermatids were allowed to activate for 15 minutes.…”

Section: Spermatid Activation Assaymentioning

confidence: 99%

See 4 more Smart Citations

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality inCaenorhabditis elegans

Hammerquist

Curran

2020

Preprint

Self Cite

View full text Add to dashboard Cite

The negative regulator of RNA polymerase (pol) III mafr-1 has been shown to affect RNA pol III transcript abundance, lipid biosynthesis and storage, progeny output, and lifespan. We deleted mafr-1 from the Caenorhabditis elegans genome and found that animals lacking mafr-1 replicated many phenotypes from previous RNAi-based studies, but strikingly not the oocyte-related reproductive phenotypes. Utilizing a yeast two-hybrid assay, we discovered several novel interactors of MAFR-1 that are expressed in a sperm-and germline-enriched manner. In support of a role for MAFR-1 in the male germline, we found mafr-1 null males have smaller spermatids that are less capable in competition for fertilization; a phenotype that was dependent on RNA pol III activity. Restoration of MAFR-1 expression specifically in the germline rescued the spermatid-related phenotypes, suggesting a cell autonomous role for MAFR-1 in nematode male fertility. Based on the high degree of conservation of Maf1 activity across species, our study may inform similar roles for Maf1 and RNA pol III in mammalian male fertility.

show abstract

Section: Mafr-1 Regulates Male Sperm Fitnessmentioning

confidence: 84%

Section: Mafr-1 Regulates Male Sperm Fitnessmentioning

confidence: 99%

Section: Mafr-1 Regulates Male Sperm Fitnessmentioning

confidence: 99%

Section: Sperm Size Analysismentioning

confidence: 99%

Section: Spermatid Activation Assaymentioning

confidence: 99%

See 3 more Smart Citations

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality inCaenorhabditis elegans

Hammerquist

Curran

2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Structural basis for the stereospecific inhibition of the dual proline/hydroxyproline catabolic enzyme ALDH4A1 by trans‐4‐hydroxy‐L‐proline

et al. 2021

View full text Add to dashboard Cite

Aldehyde dehydrogenase 4A1 (ALDH4A1) catalyzes the final steps of both proline and hydroxyproline catabolism. It is a dual substrate enzyme that catalyzes the NAD + -dependent oxidations of L-glutamate-γ-semialdehyde to L-glutamate (proline metabolism), and 4-hydroxy-L-glutamate-γ-semialdehyde to 4-erythro-hydroxy-L-glutamate (hydroxyproline metabolism). Here we investigated the inhibition of mouse ALDH4A1 by the six stereoisomers of proline and 4-hydroxyproline using steady-state kinetics and X-ray crystallography. Trans-4-hydroxy-L-proline is the strongest of the inhibitors studied, characterized by a competitive inhibition constant of 0.7 mM, followed by L-proline (1.9 mM). The other compounds are very weak inhibitors (approximately 10 mM or greater). Insight into the selectivity for L-stereoisomers was obtained by solving crystal structures of ALDH4A1 complexed with trans-4-hydroxy-L-proline and trans-4-hydroxy-D-proline. The structures suggest that the 10-fold greater preference for the L-stereoisomer is due to a serine residue that hydrogen bonds to the amine group of trans-4-hydroxy-L-proline. In contrast, the amine group of the D-stereoisomer lacks a direct interaction with the enzyme due to a different orientation of the pyrrolidine ring. These results suggest that hydroxyproline catabolism is subject to substrate inhibition by trans-4-hydroxy-L-proline, analogous to the known inhibition of proline catabolism by L-proline. Also, drugs targeting the first enzyme of hydroxyproline catabolism, by elevating the level of trans-4-hydroxy-L-proline, may inadvertently impair proline catabolism by the inhibition of ALDH4A1.

show abstract

Oolonghomobisflavans from Camellia sinensis increase Caenorhabditis elegans lifespan and healthspan

Duangjan

Curran

2021

GeroScience

Self Cite

View full text Add to dashboard Cite

Tea polyphenols are widely considered as excellent antioxidant agents which can contribute to human health and longevity. However, the identification of the active biomolecules in complex tea extracts that promote health and longevity are not fully known. Here we used the nematode Caenorhabditis elegans to analyze the health benefits and longevity effects of Camellia sinensis oolong tea extracts (QFT, NFT, and CFT) and oolonghomobisflavan A and oolonghomobisflavan B, which are present in oolong tea extracts. Our results showed that oolong tea extracts and oolonghomobisflavans prolong lifespan and improved healthspan by curtailing the age-related decline in muscle activity and the accumulation of age pigment (lipofuscin). We found that the lifespan and healthspan promoting effects of oolong tea extracts and oolonghomobisflavans were positively correlated with the stress resistance via DAF-16/FOXO transcription factor. Furthermore, oolong tea extracts and oolonghomobisflavans displayed protective effects against Aβ- and polyQ-induced neuro/proteotoxicity. Overall, our study provides new evidence to support the health benefits of oolong tea and importantly identify oolonghomobisflavans as potent bioactive molecules that promote health when supplemented with a normal diet. As such, oolonghomobisflavans represent a valuable new class of compounds that promote healthy aging.

show abstract

Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage inC. elegans

Cited by 10 publications

References 72 publications

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality inCaenorhabditis elegans

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality inCaenorhabditis elegans

Structural basis for the stereospecific inhibition of the dual proline/hydroxyproline catabolic enzyme ALDH4A1 by trans‐4‐hydroxy‐L‐proline

Oolonghomobisflavans from Camellia sinensis increase Caenorhabditis elegans lifespan and healthspan

Contact Info

Product

Resources

About