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Updated: Oct 3, 2025
Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Propofol toxicity in the developing mouse heart mitochondria
Matthew B Barajas1, Sarah D Brunner2, Aili Wang1
1Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA.
Insights
Propofol infusion syndrome (PRIS) impairs heart mitochondria in newborns by disrupting energy production. This study reveals propofol causes mitochondrial dysfunction, explaining why children are vulnerable to PRIS.
Area of Science:
- Biochemistry
- Cardiology
- Pediatrics
Background:
- Propofol infusion syndrome (PRIS) is a life-threatening condition linked to prolonged propofol use.
- Cardiac complications are common in pediatric PRIS and contribute to mortality.
- The mechanisms of propofol toxicity in developing hearts remain unclear.
Purpose of the Study:
- To investigate the specific effects of propofol on immature cardiac mitochondria.
- To determine if propofol induces mitochondrial defects in newborn cardiomyocytes.
Main Methods:
- Isolated cardiac mitochondria from newborn mice were exposed to propofol or intralipid in vitro.
- Mitochondrial respiration, membrane potential (ΔΨ), and respiratory chain complex kinetics were assessed.
- The effects of a coenzyme Q analog (CoQ0) were evaluated.
Main Results:
- Propofol induced a dose-dependent increase in proton leak and impaired substrate oxidation at coenzyme Q (CoQ).
- These mitochondrial defects prevented adequate ΔΨ generation in propofol-exposed cardiomyocytes.
- Coenzyme Q0 addition reversed propofol-induced leak and enhanced Complex II+III activity.
Conclusions:
- Propofol uncouples immature cardiomyocyte mitochondria via CoQ-sensitive proton leak.
- Propofol interferes with electron transport at the CoQ level, impairing mitochondrial function.
- These findings elucidate propofol toxicity mechanisms in the developing heart, explaining pediatric vulnerability to PRIS.
Background:
Propofol infusion syndrome (PRIS) is a potentially lethal consequence of long-term propofol administration. Children are vulnerable and cardiac involvement is often prominent and associated with mortality. We aimed to determine the mechanism of propofol toxicity in newborn mice, hypothesizing that propofol would induce discrete defects within immature cardiac mitochondria.
Methods:
Newborn murine cardiac mitochondria were exposed to propofol or intralipid in vitro. Non-exposed mitochondria served as controls. Mitochondrial respiration and membrane potential (ΔΨ) were measured and respiratory chain complex kinetics were determined.
Results:
Propofol and intralipid exerted biological activity in isolated mitochondria. Although intralipid effects were a potential confounder, we found that propofol induced a dose-dependent increase in proton leak and caused a defect in substrate oxidation at coenzyme Q (CoQ). These impairments prevented propofol-exposed cardiomyocyte mitochondria from generating an adequate ΔΨ. The addition of the quinone analog, CoQ0, blocked propofol-induced leak and increased Complex II+III activity.
Conclusions:
Propofol uncoupled immature cardiomyocyte mitochondria by inducing excessive CoQ-sensitive leak and interfered with electron transport at CoQ. The findings provide new insight into the mechanisms of propofol toxicity in the developing heart and may help explain why children are vulnerable to developing PRIS.
Impact:
Propofol uncouples immature cardiomyocyte mitochondria by inducing excessive coenzyme Q (CoQ)-sensitive proton leak. Propofol also interferes with electron transport at the level of CoQ. These defects provide new insight into propofol toxicity in the developing heart.
