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Piao, Y.; Jin, Zhehu

doi:10.1095/biolreprod.114.127191

Biology of Reproduction

2015

DOI: 10.1095/biolreprod.114.127191

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Y. Piao¹,

Zhehu Jin²

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Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

et al. 2017

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Spermatids undergo the final steps of maturation during spermiogenesis, a process that necessitates extensive rearrangement of organelles such as the mitochondria. Male infertility has been linked to mitochondrial disorder, for example, hypospermatogenesis and asthenozoospermia. However, the mechanisms that regulate mitochondrial dynamics during spermiogenesis remain largely unknown. We found the glycerol kinase (Gyk)-like proteins glycerol kinase-like 1 (Gykl1) and glycerol kinase 2 (Gk2) were specifically localized to the mitochondria in spermatids. Male mice deficient in either Gykl1 or Gk2 were infertile due to dysfunctional spermatozoa, which exhibited unregulated ATP production, disordered mitochondrial sheath formation, abnormal mitochondrial morphology, and defective sperm tail. We demonstrated that the unique C-terminal sequences found in Gykl1 and Gk2 mediated their targeting to the mitochondrial outer membrane. Furthermore, both Gykl1 and Gk2 could interact with Pld6 (MitoPLD) and induce Pld6 and phosphatidic acid (PA)-dependent mitochondrial clustering in cells. Taken together, our study has revealed previously unsuspected functions of Gyk-like proteins in spermiogenesis, providing new insight into the potential mechanisms that lead to spermatozoa dysfunction and male infertility.

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Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

et al. 2017

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West syndrome caused by homozygous variant in the evolutionary conserved gene encoding the mitochondrial elongation factor GUF1

et al. 2015

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West syndrome (WS), defined by the triad of infantile spasms, pathognomonic hypsarrhythmia and developmental regression, is a rare epileptic disease affecting about 1:3500 live births. To get better insights on the genetic of this pathology, we exomesequenced the members of a consanguineous family affected with isolated WS. We identified a homozygous variant (c.1825G4T/p.(Ala609Ser)) in the GUF1 gene in the three affected siblings. GUF1 encodes a protein essential in conditions that counteract faithful protein synthesis: it is able to remobilize stuck ribosomes and transiently inhibit the elongation process to optimize protein synthesis. The variant identified in the WS family changes an alanine residue conserved in all eukaryotic organisms and positioned within the tRNA-binding moiety of this nuclear genome-encoded mitochondrial translational elongation factor. Yeast complementation assays show that the activity of GUF1 A609S is modified in suboptimal environments. We suggest a new link between improper assembly of respiratory chain complexes and WS.

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Retractions

Cited by 2 publications

References 0 publications

Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

West syndrome caused by homozygous variant in the evolutionary conserved gene encoding the mitochondrial elongation factor GUF1

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