Exposure to urban particulate matter (UPM) impairs mitochondrial dynamics in BV2 cells, triggering a mitochondrial biogenesis response

• Published in: The Journal of physiology Vol. 602; no. 12; pp. 2737 - 2750
• Main Authors: Morris, Rebecca H., Counsell, Serena J., McGonnell, Imelda M., Thornton, Claire
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2024
• Subjects: Air pollution; Bioenergetics; biogenesis; Biosynthesis; BV2; Cardiovascular diseases; Cell survival; Intrauterine exposure; Membrane potential; microglia; Mitochondria; Neonates; Neurodevelopmental disorders; Particulate matter; Reactive oxygen species; particulate matter; air pollution; biogenesis; microglia; mitochondria; BV2
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP285978

World Health Organisation data suggest that up to 99% of the global population are exposed to air pollutants above recommended levels. Impacts to health range from increased risk of stroke and cardiovascular disease to chronic respiratory conditions, and air pollution may contribute to over 7 million premature deaths a year. Additionally, mounting evidence suggests that in utero or early life exposure to particulate matter (PM) in ambient air pollution increases the risk of neurodevelopmental impairment with obvious lifelong consequences. Identifying brain‐specific cellular targets of PM is vital for determining its long‐term consequences. We previously established that microglial‐like BV2 cells were particularly sensitive to urban (U)PM‐induced damage including reactive oxygen species production, which was abrogated by a mitochondrially targeted antioxidant. Here we extend those studies to find that UPM treatment causes a rapid impairment of mitochondrial function and increased mitochondrial fragmentation. However, there is a subsequent restoration of mitochondrial and therefore cell health occurring concomitantly with upregulated measures of mitochondrial biogenesis and mitochondrial load. Our data highlight that protecting mitochondrial function may represent a valuable mechanism to offset the effects of UPM exposure in the neonatal brain. Key points Air pollution represents a growing risk to long‐term health especially in early life, and the CNS is emerging a target for airborne particulate matter (PM). We previously showed that microglial‐like BV2 cells were vulnerable to urban (U)PM exposure, which impaired cell survival and promoted reactive oxygen species production. Here we find that, following UPM exposure, BV2 mitochondrial membrane potential is rapidly reduced, concomitant with decreased cellular bioenergetics and increased mitochondrial fission. However, markers of mitochondrial biogenesis and mitochondrial mass are subsequently induced, which may represent a cellular mitigation strategy. As mitochondria are more vulnerable in the developing brain, exposure to air pollution may represent a greater risk to lifelong health in this cohort; conversely, promoting mitochondrial integrity may offset these risks. figure legend Air pollution affects most of the planet's population. Unsurprisingly, pollution‐related chronic respiratory conditions and cardiovascular disease are becoming more prevalent, but emerging data suggest that airborne particulate matter exposure also impacts neurodevelopment and may play a role in neurodegeneration. In this study, we examine the effects of urban particulate matter (UPM) exposure on BV2 microglial‐like cells, evaluating mitochondrial structure and function. We find that mitochondrial membrane potential and cellular bioenergetics are rapidly impaired after UPM treatment. Subsequently there is an increase in markers of mitochondrial biogenesis, which may constitute a cellular mitigation strategy. Protecting mitochondrial function may be crucial in ameliorating the effects of airborne pollution exposure particularly in the developing brain where consequences are lifelong.