PUBLICATION

Leucine mediates autophagosome-lysosome fusion and improves sperm motility by activating the PI3K/Akt pathway

Authors
Zhang, J., Zhang, X., Liu, Y., Su, Z., Dawar, F.U., Dan, H., He, Y., Gui, J.F., Mei, J.
ID
ZDB-PUB-180118-17
Date
2017
Source
Oncotarget   8: 111807-111818 (Journal)
Registered Authors
Gui, Jian-Fang, He, Yan, Mei, Jie
Keywords
PI3K/Akt pathway, autophagosome-lysosome fusion, leucine, sperm motility
MeSH Terms
none
PubMed
29340093 Full text @ Oncotarget
Abstract
Amino acid supplementation is an efficient and effective strategy to increase sperm quality. In our research, a comparative study was conducted to screen free amino acids to improve sperm motility, and we found that leucine was the most efficient one. Leucine treatment increases sperm motility depending on the activation of PI3K/Akt signaling pathway, while the chemical inhibitor of PI3K/Akt signal could reduce the amount of pAkt activated by leucine treatment. Moreover, leucine treatment improved the expression of P62 and LC3-II, substantially suppressed the autophagy process in zebrafish testis. In vitro studies showed that leucine could reduce the fusion of autophagosome and lysosome that was indicated by the co-localization of EGFP-LC3 and lysosome marker. Two chemical modulators of autophagy, such as LY294002 (the inhibitor of PI3K/Akt signal) and chloroquine were administered to investigate the process of autophagy on zebrafish sperm motility. LY294002 inhibited autophagosome formation to reduced sperm motility, while chloroquine inhibited the fusion of autophagosome and lysosome to improve sperm motility. Our data suggest that short-term treatment with leucine could increase zebrafish sperm motility by affecting the autophagy and inhibiting the fusion of autophagosome and lysosomes, depending on the activation of PI3K/Akt signaling pathway.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping