What question did this study set out to answer?

The research aims to investigate how isoflurane affects protein homeostasis and contributes to postoperative delirium in the context of proteotoxicity.

February 13, 2026Open Access

Isoflurane aggravates pre-existing proteotoxicity in adult nematodes by suppressing mitochondrial fitness

Key Points

The research aims to investigate how isoflurane affects protein homeostasis and contributes to postoperative delirium in the context of proteotoxicity.
Utilized the nematode C. elegans for experimental model
Assessed impact of isoflurane on protein homeostasis
Evaluated roles of DAF-16/FOXO and SKN-1/NRF transcription factors
Investigated mitophagy components and their effects on proteotoxicity
Examined mitochondrial biogenesis induction to mitigate protein aggregation effects.
Isoflurane exposure leads to a decline in proteostasis in adult C. elegans
Proteostasis impairments are linked to aging-regulating transcription factors
Knockdown of mitophagy components alleviates isoflurane-induced effects
Induction of mitochondrial biogenesis protects against protein aggregation challenges
Findings suggest a potential connection between isoflurane and postoperative delirium through proteotoxicity.

Abstract

Post operative delirium (POD) is an acute complication, characterized by fluctuating attention and confusion, which may develop and persist into cognitive decline. POD is most commonly observed in elderly patients, particularly those with preexisting cognitive impairments. Isoflurane, a widely used volatile anesthetic, is associated with POD. However. how exposure to isoflurane affects the integrity of the proteome is largely obscure. Utilizing the nematode C. elegans, we found that isoflurane leads to a long-lasting decline in protein homeostasis (proteostasis) of adult animals that express neurodegeneration-causing, abnormally long poly-glutamine stretches. Isoflurane-induced proteostasis impairments are dependent on the aging-regulating transcription factors DAF-16/FOXO and SKN-1/NRF, and can be alleviated by the knockdown of certain components of the mitophagy mechanism. Accordingly, induction of mitochondrial biogenesis protects worms that are challenged by protein aggregation from isoflurane-induced proteotoxicity. Our observations provide novel insights into the mechanism that links isoflurane, proteotoxicity and POD, and highlight the potential of mitophagy modulators as alleviators of POD.

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