Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

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Abstract

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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Cancer Statistics, 2021

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

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PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.

Vamsi K Mootha, Cecilia M. Lindgren, Karl-Fredrik Eriksson … (2003)

DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.

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Author and article information

Contributors

Yang Yang:

ORCID: http://orcid.org/0000-0002-1163-2359

yang200214yy@nwu.edu.cn

Journal

Journal ID (nlm-ta): Signal Transduct Target Ther

Journal ID (iso-abbrev): Signal Transduct Target Ther

Title: Signal Transduction and Targeted Therapy

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-9907

ISSN (Electronic): 2059-3635

Publication date (Electronic): 1 March 2024

Publication date PMC-release: 1 March 2024

Publication date Collection: 2024

Volume: 9

Electronic Location Identifier: 50

Affiliations

[1 ]Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, ( https://ror.org/00z3td547) Xi’an, 710021 China

[2 ]Xi’an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine, Northwest University, ( https://ror.org/00z3td547) 229 Taibai North Road, Xi’an, 710069 China

[3 ]Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, ( https://ror.org/02tbvhh96) 277 Yanta West Road, Xi’an, 710061 China

[4 ]Department of Cardiothoracic Surgery, The First Affiliated Hospital of Zhengzhou University, ( https://ror.org/056swr059) 1 Jianshe East, Zhengzhou, 450052 China

[5 ]Department of Hematology, The First Affiliated Hospital of Xi’an Jiaotong University, ( https://ror.org/02tbvhh96) 277 Yanta West Road, Xi’an, 710061 China

Author information

Yang Yang http://orcid.org/0000-0002-1163-2359

Article

Publisher ID: 1756

DOI: 10.1038/s41392-024-01756-w

PMC ID: 10904817

PubMed ID: 38424050

SO-VID: 06e09862-4592-4967-bf98-c19c731a4540

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 25 September 2023

Date revision received : 13 January 2024

Date accepted : 23 January 2024

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Keywords: pathogenesis,diseases

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Keywords: pathogenesis, diseases

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Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

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Most cited references 694

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Cancer Statistics, 2021

PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.

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