Transcriptional Integration of Mitochondrial Biogenesis

Overview

Journal Trends Endocrinol Metab

Specialty Endocrinology

Date 2012 Jul 24

PMID 22817841

Citations 393

Authors

Richard C Scarpulla

Rick B Vega

Daniel P Kelly

Affiliations

Soon will be listed here.

Abstract

Gene regulatory factors encoded by the nuclear genome are essential for mitochondrial biogenesis and function. Some of these factors act exclusively within the mitochondria to regulate the control of mitochondrial transcription, translation, and other functions. Others govern the expression of nuclear genes required for mitochondrial metabolism and organelle biogenesis. The peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family of transcriptional coactivators play a major role in transducing and integrating physiological signals governing metabolism, differentiation, and cell growth to the transcriptional machinery controlling mitochondrial functional capacity. Thus, the PGC-1 coactivators serve as a central component of the transcriptional regulatory circuitry that coordinately controls the energy-generating functions of mitochondria in accordance with the metabolic demands imposed by changing physiological conditions, senescence, and disease.

Citing Articles

Fam163a knockdown and mitochondrial stress in the arcuate nucleus of hypothalamus reduce AgRP neuron activity and differentially regulate mitochondrial dynamics in mice.

Erdogan C, Yavuz Y, Ozgun H, Bilgin V, Agus S, Kalkan U Acta Physiol (Oxf). 2025; 241(4):e70020.

PMID: 40071489 PMC: 11897941. DOI: 10.1111/apha.70020.

PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos.

Idrees M, Haider Z, Perera C, Ullah S, Lee S, Lee S Front Cell Dev Biol. 2025; 12:1531378.

PMID: 39897080 PMC: 11782182. DOI: 10.3389/fcell.2024.1531378.

Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis.

Wang J, Jia D, Zhang Z, Wang D Metabolites. 2025; 15(1).

PMID: 39852400 PMC: 11767263. DOI: 10.3390/metabo15010059.

eIF2α phosphorylation-ATF4 axis-mediated transcriptional reprogramming mitigates mitochondrial impairment during ER stress.

Thi Le H, Yu J, Ahn H, Kim M, Chae I, Cho H Mol Cells. 2025; 48(2):100176.

PMID: 39756584 PMC: 11786836. DOI: 10.1016/j.mocell.2024.100176.

Connecting dots of long COVID-19 pathogenesis: a vagus nerve- hypothalamic-pituitary- adrenal-mitochondrial axis dysfunction.

Camici M, Del Duca G, Brita A, Antinori A Front Cell Infect Microbiol. 2024; 14:1501949.

PMID: 39735263 PMC: 11671747. DOI: 10.3389/fcimb.2024.1501949.

References

Narkar V, Fan W, Downes M, Yu R, Jonker J, Alaynick W . Exercise and PGC-1α-independent synchronization of type I muscle metabolism and vasculature by ERRγ. Cell Metab. 2011; 13(3):283-93. PMC: 3084588. DOI: 10.1016/j.cmet.2011.01.019. View

Kim J, Kundu M, Viollet B, Guan K . AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011; 13(2):132-41. PMC: 3987946. DOI: 10.1038/ncb2152. View

Dufour C, Wilson B, Huss J, Kelly D, Alaynick W, Downes M . Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma. Cell Metab. 2007; 5(5):345-56. DOI: 10.1016/j.cmet.2007.03.007. View

Larsson N, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M . Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet. 1998; 18(3):231-6. DOI: 10.1038/ng0398-231. View

Grivennikov S, Greten F, Karin M . Immunity, inflammation, and cancer. Cell. 2010; 140(6):883-99. PMC: 2866629. DOI: 10.1016/j.cell.2010.01.025. View

Gleyzer N, Vercauteren K, Scarpulla R . Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol. 2005; 25(4):1354-66. PMC: 548005. DOI: 10.1128/MCB.25.4.1354-1366.2005. View

Scarpulla R . Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress. Biochim Biophys Acta. 2011; 1819(9-10):1088-97. PMC: 3306451. DOI: 10.1016/j.bbagrm.2011.10.011. View

Seidel-Rogol B, McCulloch V, Shadel G . Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop. Nat Genet. 2002; 33(1):23-4. DOI: 10.1038/ng1064. View

Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O . Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005; 1(4):259-71. DOI: 10.1016/j.cmet.2005.03.002. View

10.

Fisher R, Clayton D . Purification and characterization of human mitochondrial transcription factor 1. Mol Cell Biol. 1988; 8(8):3496-509. PMC: 363587. DOI: 10.1128/mcb.8.8.3496-3509.1988. View

11.

LEHMAN J, Barger P, Kovacs A, Saffitz J, Medeiros D, Kelly D . Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 2000; 106(7):847-56. PMC: 517815. DOI: 10.1172/JCI10268. View

12.

Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y . Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One. 2010; 5(7):e11707. PMC: 2908542. DOI: 10.1371/journal.pone.0011707. View

13.

Sonoda J, Mehl I, Chong L, Nofsinger R, Evans R . PGC-1beta controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis. Proc Natl Acad Sci U S A. 2007; 104(12):5223-8. PMC: 1829290. DOI: 10.1073/pnas.0611623104. View

14.

Verdin E, Hirschey M, Finley L, Haigis M . Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem Sci. 2010; 35(12):669-75. PMC: 2992946. DOI: 10.1016/j.tibs.2010.07.003. View

15.

Eichner L, Giguere V . Estrogen related receptors (ERRs): a new dawn in transcriptional control of mitochondrial gene networks. Mitochondrion. 2011; 11(4):544-52. DOI: 10.1016/j.mito.2011.03.121. View

16.

Morrish F, Giedt C, Hockenbery D . c-MYC apoptotic function is mediated by NRF-1 target genes. Genes Dev. 2003; 17(2):240-55. PMC: 195978. DOI: 10.1101/gad.1032503. View

17.

Grivennikov S, Karin M . Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev. 2009; 20(1):65-71. PMC: 2821983. DOI: 10.1016/j.gde.2009.11.004. View

18.

Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M . Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature. 2010; 464(7293):1313-9. DOI: 10.1038/nature08991. View

19.

Gatenby R, Gillies R . Why do cancers have high aerobic glycolysis?. Nat Rev Cancer. 2004; 4(11):891-9. DOI: 10.1038/nrc1478. View

20.

Handschin C, Spiegelman B . Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev. 2006; 27(7):728-35. DOI: 10.1210/er.2006-0037. View