2. Academic Validation
  3. Ultrafine black carbon caused mitochondrial oxidative stress, mitochondrial dysfunction and mitophagy in SH-SY5Y cells

Ultrafine black carbon caused mitochondrial oxidative stress, mitochondrial dysfunction and mitophagy in SH-SY5Y cells

  • Sci Total Environ. 2022 Mar 20;813:151899. doi: 10.1016/j.scitotenv.2021.151899.
Yu Shang 1,  Wanlei Xue 2,  Jiexing Kong 2,  Yingjun Chen 3,  Xinghua Qiu 4,  Xingqin An 5,  Yi Li 5,  Hongli Wang 6,  Jing An 7
Affiliations

Affiliations

  • 1 School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; State Environmental Protection Key Laboratory of Formation and Prevention of Urban Air Pollution Complex, Shanghai Academy of Environment Sciences, Shanghai 200233, China.
  • 2 School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
  • 3 Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China.
  • 4 BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China.
  • 5 State Key Laboratory of Severe Weather & Key Laboratory of Atmospheric Chemistry of CMA, Chinese Academy of Meteorological Sciences, Beijing 100081, China.
  • 6 State Environmental Protection Key Laboratory of Formation and Prevention of Urban Air Pollution Complex, Shanghai Academy of Environment Sciences, Shanghai 200233, China.
  • 7 School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China. Electronic address: [email protected].
PMID: 34838543 DOI: 10.1016/j.scitotenv.2021.151899
Abstract

Exposure to ambient ultrafine black carbon (uBC, with aerodynamic diameter less than 100 nm) is associated with many neurodegenerative diseases. Oxidative stress is the predominantly reported neurotoxic effects caused by uBC exposure. Mitochondrion is responsible for production of majority of ROS in cells and mitochondrial dysfunction is closely related to adverse nervous outcomes. Mitophagy is an important cellular process to eliminate dysfunctional or damaged mitochondria. However, the mechanisms that modulate Mitophagy and mitochondrial dysfunction initiated by uBC remain to be elucidated. The purpose of this study was to investigate how mitochondrial oxidative stress regulated mitochondrial dysfunction and Mitophagy in human neuroblastoma cell line (SH-SY5Y) after uBC treatment. RNA interference was further applied to explore the roles of Mitophagy in mitochondrial dysfunction. We found uBC triggered cell Apoptosis via ROS-mitochondrial apoptotic pathway. The uBC also caused serious mitochondrial damage and respiratory dysfunction, indicated by the abnormalities in mitochondrial division and fusion related proteins, decreased mitochondria number and ATP level. Increased PTEN induced putative kinase 1 (PINK1) and Parkin protein levels and the autolysosome numbers suggested uBC could promote Pink1/Parkin-dependent Mitophagy process in SH-SY5Y cells. Mitophagy inhibition could reserve mitochondria number and ATP activity, but not fusion and division related protein levels in SH-SY5Y cells exposed to uBC. Administration of a mitochondria-targeted antioxidant (mitoquinone) significantly eliminated uBC caused Apoptosis, mitochondrial dysfunction and Mitophagy. Our data suggested mitochondrial oxidative stress regulated uBC induced mitochondrial dysfunction and PINK1/Parkin-dependent Mitophagy. PINK1/Parkin-dependent Mitophagy probably participated in regulating uBC caused mitochondrial dysfunction but not by controlling mitochondrial fusion and division related proteins. Our results may provide some new insights and evidences to understand the mechanisms of neurotoxicity induced by uBC.

Keywords

Air pollution; Mitochondrial dysfunction; Mitophagy; Oxidative stress; Ultrafine black carbon.

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