Screening platform for the identification of molecular targets involved in mitochondrial homeostasis

• Grant number: 19/11171-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 26, 2019
• End date: October 25, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Leonardo dos Reis Silveira
• Grantee: Tanes Imamura de Lima
• Supervisor: Johan Auwerx
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: École Polytechnique Fédérale de Lausanne (EPFL), Switzerland
• Associated to the scholarship: 17/21628-9 - High throughput screening (HTS) biological platform for mitochondrial homeostasis evaluation in adherent cells, BP.PD

Abstract

The molecular control of mitochondrial function represents a fundamental aspect of mammalian physiology and defects in the integrity of this system can lead to severe perturbations to cell homeostasis giving rise to a broad range of pathologies, including obesity and type 2 diabetes. The main goal of this project is to develop an integrated screening platform for the identification of transcriptional modulators involved in mitochondrial homeostasis. The approach focuses on the combination of bioinformatics, bioenergetics, and molecular assays to screen potential targets. Through this integrated platform, we expect to identify uncharacterized transcription factors involved in the regulation of mitochondrial function by screening previously promoter-based selected candidates from our laboratory (Scientific report, Thematic project-16/23008-5) and potential candidates from bioinformatics analysis of the BXD mouse genetic reference population (Auwerx lab). Finally, we hope that this screening platform can be used to generate findings with significant impact in the field of metabolism and mitochondrial biology and ultimately contribute to the development of alternative therapies for metabolic diseases such as obesity and type 2 diabetes.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LIMA, TANES; LI, TERYTTY YANG; MOTTIS, ADRIENNE; AUWERX, JOHAN. Pleiotropic effects of mitochondria in aging. NATURE AGING, v. 2, n. 3, p. 15-pg., 2022-03-01. (19/11171-7)

ROMANI, MARIO; SORRENTINO, VINCENZO; OH, CHANG-MYUNG; LI, HAO; DE LIMA, TANES IMAMURA; ZHANG, HONGBO; SHONG, MINHO; AUWERX, JOHAN. NAD(+) boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle. CELL REPORTS, v. 34, n. 3, JAN 19 2021. (19/11171-7)

ZANOU, NADEGE; DRIDI, HAIKEL; REIKEN, STEVEN; DE LIMA, TANES IMAMURA; DONNELLY, CHRIS; DE MARCHI, UMBERTO; FERRINI, MANUELE; VIDAL, JEREMY; SITTENFELD, LEAH; FEIGE, JEROME N.; et al. Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity. NATURE COMMUNICATIONS, v. 12, n. 1, DEC 10 2021. (19/11171-7)

LIMA, TANES I.; LAURILA, PIRKKA-PEKKA; WOHLWEND, MARTIN; MOREL, JEAN DAVID; GOEMINNE, LUDGER J. E.; LI, HAO; ROMANI, MARIO; LI, XIAOXU; OH, CHANG-MYUNG; PARK, DOHYUN; et al. Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging. Science Translational Medicine, v. 15, n. 696, p. 14-pg., 2023-05-17. (19/11171-7, 13/07607-8, 16/23008-5, 19/22512-0)