Journal article
The Interplay Between Mitochondrial Reactive Oxygen Species, Endoplasmic Reticulum Stress, and Nrf2 Signaling in Cardiometabolic Health
Antioxidants & redox signaling, Vol.35(4), pp.252-269
08/01/2021
DOI: 10.1089/ars.2020.8220
PMCID: PMC8262388
PMID: 33599550
Abstract
Significance: Mitochondria-derived reactive oxygen species (mtROS) are by-products of normal physiology that may disrupt cellular redox homeostasis on a regular basis. Nonetheless, failure to resolve sustained mitochondrial stress to mitigate high levels of mtROS might contribute to the etiology of numerous pathological conditions, such as obesity, insulin resistance, and cardiovascular disease (CVD).
Recent Advances: Notably, recent studies have demonstrated that moderate mitochondrial stress might result in the induction of different stress response pathways that ultimately improve the organism's ability to deal with subsequent stress, a process termed mitohormesis. mtROS have been shown to play a key role in regulating this adaptation.
Critical Issue: mtROS regulate the convergence of different signaling pathways that, when disturbed, might impair cardiometabolic health. Conversely, mtROS seem to be required to mediate activation of prosurvival pathways, contributing to improved cardiometabolic fitness. In the present review, we will primarily focus on the role of mtROS in the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and examine the role of endoplasmic reticulum (ER) stress in coordinating the convergence of ER stress and oxidative stress signaling through activation of Nrf2 and activating transcription factor 4 (ATF4).
Future Directions: The mechanisms underlying cardiometabolic protection in response to mitochondrial stress have only started to be investigated. Integrated understanding of how mtROS and ER stress cooperatively promote activation of prosurvival pathways might shed mechanistic insight into the role of mitohormesis in mediating cardiometabolic protection and might inform future therapeutic avenues for the treatment of metabolic diseases contributing to CVD.
Details
- Title: Subtitle
- The Interplay Between Mitochondrial Reactive Oxygen Species, Endoplasmic Reticulum Stress, and Nrf2 Signaling in Cardiometabolic Health
- Creators
- Sarah Hartwick Bjorkman - Univ Iowa, Fraternal Order Eagles Diabet Res Ctr, 169 Newton Rd,4312 PBDB, Iowa City, IA 52242 USARenata Oliveira Pereira - Univ Iowa, Fraternal Order Eagles Diabet Res Ctr, 169 Newton Rd,4312 PBDB, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.35(4), pp.252-269
- Publisher
- Mary Ann Liebert, Inc
- DOI
- 10.1089/ars.2020.8220
- PMID
- 33599550
- PMCID
- PMC8262388
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Number of pages
- 18
- Grant note
- T32DK112751-01 / Diabetes Research Training Program - National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1R01DK125405-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 08/01/2021
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984420844502771
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