The study of the impact of LIPL-5 deficiency on the endoplasmic reticulum UPR and its relationship with the mitochondrial activity of Caenorhabiditis elegans

• Grant number: 21/05350-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Fernanda Marques da Cunha
• Grantee: Carolina Gomes de Assis
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 25/03832-4 - Generation of strains for conditional degradation of ER proteins ATF-6 and PEK-1 in Caenorhabditis elegans, BE.EP.DR

Abstract

The endoplasmic reticulum (ER) UPR is an adaptive response of the organism that through specific molecular pathways acts to reestablish cell homeostasis in stressful situations. In a previous work by the group, it was observed that the deficiency of the lipase LIPL-5 caused changes in the C. elegans lipidome, increasing the amount of cardiolipins, coenzyme Q9 and some types of ceramide, sphingomyelin and cholesterol of the animal. The mutation also affected the mitochondrial phenotype, increasing the mitochondria's ability to oxidize NADH and lipids. Preliminary data from the group revealed that the silencing of lipl-5 seems to impair the animal's ability to activate the UPRre against reticulum stress induced by tunimicamycin, in addition to discreetly activating the UPRmt. ER and mitochondria interact physically and functionally and this interaction is fundamental to the cellular response to stressful situations. In addition, it is known that the interaction of ER with mitochondria has a profound impact on biology and mitochondrial activity. Although these facts are already known, the molecular mechanisms by which ER detects and signals changes in the proteome and lipidome and the consequences of this for mitochondrial bioenergetics are not fully understood. Given these facts, it is important to investigate the impact of LIPL-5 deficiency on UPRre and its relationship with mitochondrial activity. Understanding these issues will lead to a better understanding of the biological functions of LIPL-5, and may also reveal new molecular mechanisms to control UPRre and/or the interaction between ER and mitochondria in C. elegans.