Identification and functional characterization of protein bound to NCoR1 complex and associated with molecular control of mitochondrial biogenesis process

• Grant number: 16/23008-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: August 01, 2017
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Leonardo dos Reis Silveira
• Grantee: Leonardo dos Reis Silveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Ana Carolina Migliorini Figueira ; Aníbal Eugênio Vercesi ; José Xavier Neto ; Marcio Chaim Bajgelman ; Paulo Sergio Lopes de Oliveira ; Richard C Scarpulla ; Valentina Perissi
• Associated scholarship(s): 18/20581-1 - Identification and functional characterization of protein bound to NCoR1 complex and associated with molecular control of mitochondrial biogenesis process., BP.PD; 17/21628-9 - High throughput screening (HTS) biological platform for mitochondrial homeostasis evaluation in adherent cells, BP.PD; 17/24795-3 - Search and characterization of novel transcriptional regulators of mitochondrial biogenesis associated genes, BP.DR; 17/25168-2 - Molecular control of HIF1-A expression and response to insulin mediated by PPAR in muscle cells, BP.IC

Abstract

Skeletal muscle uses a well-regulated transcriptional programs to adapt to environmental inputs through storage or consumption of energy. PPAR² plays a critical role in this process being regulated by its interaction with positive and negative co-regulators. Under NCoR1 overexpression, a well-known PPAR inhibitor, we observed a marked repression of mitochondrial biogenesis in C2C12 cells during the differentiation process. This effect was demonstrated to reduce mitochondrial respiration, mitochondrial content, oxidative proteins, tricarboxylic acid cycle intermediates and to increase glycolysis activity. In addition, this phenotype was consistent with reduced transcription of a wide spectrum of genes associated with mitochondrial metabolism as determined by RNAseq technique. However, it is unclear who are the players, which interact with NCoR1 during its repression activity over PPAR². More interesting, is the question if NCor1 could interacting with other molecular target regulating mitochondrial biogenesis by a mechanism independent of PPAR. Therefore, considering the NCoR1 effect over mitochondrial metabolism we raised the hypothesis that NCoR1 could works as very promising tool on discovery new molecular target(s) to control of mitochondrial biogenesis process in skeletal muscle cells. (AU)

Scientific publications

(8)

(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, I, TANES; SILVEIRA, LEONARDO R.. A microplate assay for measuring cell death in C2C12 cells. BIOCHEMISTRY AND CELL BIOLOGY, v. 96, n. 5, p. 702-706, OCT 2018. (16/23008-5)

SILVEIRA, LEONARDO R.; PAULETTI, BIANCA A.; LEME, ADRIANA F. PAES; LIMA, TANES I.. Seeking new molecular targets to control mitochondrial biogenesis. FASEB JOURNAL, v. 32, n. 1, p. 2-pg., 2018-04-01. (16/23008-5, 13/22733-0)

LIMA, TANES I.; VALENTIM, RAFAEL R.; ARAUJO, HYGOR N.; OLIVEIRA, ANDRE G.; FAVERO, BIANCA C.; MENEZES, EVELINE S.; ARAUJO, RAFAELA; SILVEIRA, LEONARDO R.. Role of NCoR1 in mitochondrial function and energy metabolism. Cell Biology International, v. 42, n. 6, p. 8-pg., 2018-06-01. (16/23008-5)

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)

LIMA, TANES I.; VALENTIM, RAFAEL R.; ARAUJO, HYGOR N.; OLIVEIRA, ANDRE G.; FAVERO, BIANCA C.; MENEZES, EVELINE S.; ARAUJO, RAFAELA; SILVEIRA, LEONARDO R.. Role of NCoR1 in mitochondrial function and energy metabolism. Cell Biology International, v. 42, n. 6, SI, p. 734-741, JUN 2018. (16/23008-5)

ARAUJO, HYGOR N.; LIMA, I, TANES; GUIMARAES, DIMITRIUS SANTIAGO P. S. F.; OLIVEIRA, ANDRE G.; FAVERO-SANTOS, BIANCA C.; BRANCO, RENATO C. S.; DA SILVA ARAUJO, RAFAELA MARIANO; DANTAS, ALVARO F. B.; CASTRO, ALEX; CHACON-MIKAHIL, MARA PATRICIA T.; et al. Regulation of Lin28a-miRNA let-7b-5p pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, v. 319, n. 3, p. C541-C551, SEP 2020. (13/22733-0, 16/23008-5)

LIMA, TANES I.; GUIMARAES, DIMITRIUS SANTIAGO P. S. F.; OLIVEIRA, ANDRE G.; ARAUJO, HYGOR; SPONTON, CARLOS H. G.; SOUZA-PINTO, NADJA C.; SAITO, ANGELA; FIGUEIRA, ANA CAROLINA M.; PALAMETA, SOLEDAD; BAJGELMAN, MARCIO CHAIM; et al. Opposing action of NCoR1 and PGC-1 alpha in mitochondrial redox homeostasis. Free Radical Biology and Medicine, v. 143, p. 203-208, NOV 1 2019. (16/23008-5, 17/21628-9, 17/04377-2)

SILVEIRA, LEONARDO R.; OLIVEIRA, ANDRE G.; LIMA, TANES I.; GUIMARAES, DIMITRIUS S. P.; FAVERO, BIANCA C.; ARAUJO, HYGOR N.; ARAUJO, RAFAELA. Characterization of the NCoR1 complex and its association with the molecular control of the mitochondrial biogenesis process. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (16/23008-5)