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

• Published in: Molecular and cellular biology Vol. 34; no. 13; pp. 2499 - 2516
• Main Authors: Láscarez-Lagunas, L. I., Silva-García, C. G., Dinkova, T. D., Navarro, R. E.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.07.2014; American Society for Microbiology
• Subjects: Animals; Apoptosis - genetics; Apoptosis Regulatory Proteins - genetics; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - biosynthesis; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Calcium-Binding Proteins - genetics; Caspases - genetics; Down-Regulation; E2F Transcription Factors - genetics; Gene Expression Regulation; Germ Cells - pathology; Membrane Proteins - genetics; Protein Biosynthesis - genetics; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Repressor Proteins - genetics; Repressor Proteins - metabolism; Ribosomes - metabolism; RNA Interference; RNA, Messenger - biosynthesis; RNA, Small Interfering; Stress, Physiological; Transcription Factors - genetics
• ISSN: 1098-5549; 0270-7306; 1098-5549
• DOI: 10.1128/MCB.01532-13

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.