Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
Open accessAbstract
Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca 2+ , etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca 2+ ). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Within mitochondria, the main sites of superoxide production are localized to electron transport chain complexes I and III.
“Within the mitochondria, the main sites of superoxide production have been localized to the electron transport chain (ETC) complexes I (C I) and Ⅲ [6–9].”
From Honokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans (2017) · cites this paper as [9]
The review identifies complexes I and III as sites of mitochondrial superoxide production, but it does not establish that they are generally the main sites. In “Under normal conditions” (page unavailable), it says complex I becomes a major source under pathological conditions rather than healthy resting conditions; “C. Complex III” (page unavailable) says its role in substantial physiological ROS production remains uncertain. (LLM, conf=0.88)
Experimental — accuracy not yet measuredC I exhibits only minimal ROS production with NADH-linked substrates, but addition of rotenone results in a significant increase in its rate.
“It is driven by NADH-linked substrates, C I exhibits only minimal ROS production, but the addition of a ubiquinone-site inhibitor, such as rotenone, results in a significant increase in its rate [7–9].”
From Honokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans (2017) · cites this paper as [9]
Current research has advanced knowledge on how different systems can influence NO/ROS generation from other sources, termed ROS-induced ROS release.
“Current research has greatly advanced our knowledge on how different systems can influence the NO/ROS generation from other sources in which it has been termed ROS-induced ROS release (1066, 1069).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1066]
mtROS production is actively triggered by a number of different stimuli including recognition of pathogens and PAMPs or endogenous molecules such as TNF.
“In recent years, however, several studies have shown that mtROS production is actively triggered by a number of different stimuli including the recognition of pathogens and pathogen-associated molecular patterns (PAMPs) [30,61] or endogenous molecules such as TNF [48,136].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [136]
mROS released by activation of mPTP at one mitochondrial site may activate mPTP at an adjacent site, creating a propagating wave of mPTP opening across the cell.
“The mROS released by the activation of mPTP at one mitochondrial site may activate mPTP at an adjacent site and this second opening can then trigger opening at other sites, creating a propagating wave of mPTP opening across the cell [54].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [54]
Absence of one or more peroxisomal functions can indirectly increase intracellular ROS because accumulation of compounds such as VLCFAs could be linked to disturbances in mitochondrial integrity, which secondarily increases ROS production.
“Furthermore, the absence of one or more peroxisomal functions can indirectly increase the level of intracellular ROS, because under such conditions, the accumulation of particular compounds such as VLCFAs could be linked to disturbances in mitochondrial integrity, which secondarily increases the production rate of ROS [43,44].”
From Peroxisomes in brain development and function (2016) · cites this paper as [44]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 515 · Cited by 5,383
Research works printed but not linked: 5
- [365]Saks V, Dzeja PP, Guzun R, Aliev MK, Vndeli M, Terzic A, Wallimann T. System Analysis of Cardiac Energetics-Excitation-Contraction Coupling. Integration of Mitochondrial Respiration. Darmstadt: Wiley-VCH Verlag, 2007, p. 367–405 [Google Scholar]
- [366]Salet C, Moreno G. Photosensitization of mitochondria. Molecular and cellular aspects. J Photochem Photobiol B 5: 133–150, 1990 [DOI] [PubMed] [Google Scholar]
- [425]Stokes AH, Hastings TG, Vrana KE. Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55: 659–665, 1999 [DOI] [PubMed] [Google Scholar]
- [435]Territo PR, Mootha VK, French SA, Balaban RS. Ca2+ activation of heart mitochondrial oxidative phosphorylation: role of the F0/F1-ATPase. Am J Physiol Cell Physiol 278: C423–C435, 2000 [DOI] [PubMed] [Google Scholar]
- [498]Zorov DB, Plotnikov EY, Jankauskas SS, Isaev NK, Silachev DN, Zorova LD, Pevzner IB, Pulkova NV, Zorov SD, Morosanova MA. The phenoptosis problem: what is causing the death of an organism? Biochemistry 77: 742–753, 2012 [DOI] [PubMed] [Google Scholar]
- Authors
- Zorov, D. B., Juhaszova, M., & Sollott, S. J.
- Affiliations
- National Institutes of Health (US)
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2014-07
- Volume
- 94
- Issue
- 3
- Pages
- 909-950
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- PMC
- PMC4101632
- OpenAlex
- W2076598575
- Cited by
- 5,383
- References
- 515
- Citations by year
- 2026: 571 · 2025: 778 · 2024: 743 · 2023: 708 · 2022: 697 · 2021: 532 · 2020: 428 · 2019: 295 · 2018: 246 · 2017: 174 · 2016: 111 · 2015: 82 · 2014: 14
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiological Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- mitochondrial reactive oxygen species, mitochondrial permeability transition pore, mitochondrial redox homeostasis, redox stress, mitochondrial ROS production, mitochondrial calcium, mitochondrial cell death, ischemic injury, aging
- MeSH terms
- Mitochondrial Permeability Transition Pore, Animals, Calcium, Humans, Mitochondria, Reactive Oxygen Species, Oxidative Stress, Mitochondrial Diseases, Mitochondrial Membrane Transport Proteins, Membrane Potential, Mitochondrial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
