LIN-35/Rb Causes Starvation-Induced Germ Cell Apoptosis via CED-9/Bcl2 Downregulation in Caenorhabditis elegans

Abstract

Apoptosis is an important mechanism for maintaining germ line health. In Caenorhabditis elegans, germ cell apoptosis occurs under normal conditions to sustain gonad homeostasis and oocyte quality. Under stress, germ cell apoptosis can be triggered via different pathways, including the following: (i) the CEP-1/p53 pathway, which induces germ cell apoptosis when animals are exposed to DNA damage; (ii) the mitogen-activated protein kinase kinase (MAPKK) pathway, which triggers germ cell apoptosis when animals are exposed to heat shock, oxidative stress, or osmotic stress; and (iii) an unknown mechanism that triggers germ cell apoptosis during starvation. Here, we address how starvation induces germ cell apoptosis. Using polysomal profiling, we found that starvation for 6 h reduces the translationally active ribosomes, which differentially affect the mRNAs of the core apoptotic machinery and some of its regulators. During starvation, lin-35/Rb mRNA increases its expression, resulting in the accumulation of this protein. As a consequence, LIN-35 downregulates the expression of the antiapoptotic gene ced-9/Bcl-2. We observed that the reduced translation of ced-9/Bcl-2 mRNA during food deprivation together with its downregulation drastically affects its protein accumulation. We propose that CED-9/Bcl-2 downregulation via LIN-35/Rb triggers germ cell apoptosis in C. elegans in response to starvation.

ACKNOWLEDGMENTS

This work was supported by grants from PAPIIT-UNAM (IN225509 and IN207412) and CONACYT-MEXICO (50896-Q and 103856-Q). L.I.L.-L. received a Ph.D. fellowship from CONACYT-México and PAPIIT-UNAM (IN207412). All strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440).

We thank L. Silvia Salinas, Ana Valeria Martínez Silva, and Carlos Alberto Contreras Paredes for technical assistance. We are grateful to Jorge Ramírez, Lorena Chávez-González, Simón Guzmán-León, and José Luis Santillán-Torres at the Unidad de Microarreglos, Universidad Nacional Autónoma de México, for technical support.