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Updated: Feb 10, 2026
Analysis of Oxidative Stress in Zebrafish Embryos
Published on: July 7, 2014
Oxidative stress impairs autophagy through oxidation of ATG3 and ATG7
1a Cardiovascular Division, King's College London, The British Heart Foundation Centre of Excellence , The Rayne Institute, St Thomas' Hospital , London , UK.
Abstract:
Dysfunctional macroautophagy/autophagy has been causatively linked to aging and the pathogenesis of many diseases, which are also broadly characterized by dysregulated cellular redox. As the autophagy-related (ATG) conjugation systems that mediate autophagosome maturation are cysteine dependent, their oxidation may account for loss in this catabolic process under conditions of oxidative stress. During active autophagy, LC3 is transferred from the catalytic thiol of ATG7 to the active site thiol of ATG3, where it is conjugated to phosphatidylethanolamine. In our recent study, we show LC3 is bound to the catalytic thiols of inactive ATG3 and ATG7 through a stable thioester, which becomes transient upon autophagy stimulation. Transient interaction with LC3 exposes the catalytic thiols on ATG3 and ATG7, which under pro-oxidizing conditions undergo inhibitory oxidation. This process was found to be upregulated in aged mouse tissue and therefore may account, at least in part, for impaired autophagy observed during aging.
Insights
Impaired autophagy in aging is linked to oxidative stress. Our study reveals that oxidation of ATG3 and ATG7 proteins inhibits autophagy, a process accelerated in aged tissues.
Area of Science:
- Cellular Biology
- Biochemistry
- Aging Research
Background:
- Dysfunctional macroautophagy (autophagy) is implicated in aging and various diseases.
- Cellular redox imbalance is a common feature of these conditions.
- Autophagy-related (ATG) conjugation systems, crucial for autophagosome maturation, rely on cysteine residues and are susceptible to oxidation.
Purpose of the Study:
- To investigate the impact of oxidative stress on ATG conjugation systems.
- To elucidate the mechanism by which autophagy is impaired during aging.
Main Methods:
- Analysis of LC3 interaction with ATG3 and ATG7.
- Investigation of thioester bond dynamics during autophagy.
- Assessment of protein oxidation under pro-oxidizing conditions.
- Examination of aged mouse tissues.
Main Results:
- LC3 forms a stable thioester bond with inactive ATG3 and ATG7 catalytic thiols.
- Autophagy stimulation renders this thioester bond transient, exposing catalytic thiols.
- Pro-oxidizing conditions lead to inhibitory oxidation of these exposed thiols.
- This inhibitory oxidation is elevated in aged mouse tissues.
Conclusions:
- Oxidation of ATG3 and ATG7 catalytic thiols is a mechanism for autophagy inhibition under oxidative stress.
- This oxidation process contributes to the age-related decline in autophagy.
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