Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca2+ channel-mediated PGC-1α/ERRα activation

Yoon Kyung Choi, Joon Ha Park, Yi Yong Baek, Moo Ho Won, Dooil Jeoung, Hansoo Lee, Kwon Soo Ha, Young Guen Kwon, Young Myeong Kim

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38 Citations (Scopus)


Carbon monoxide (CO), derived by the enzymatic reaction of heme oxygenase (HO), is a cellular regulator of energy metabolism and cytoprotection; however, its underlying mechanism has not been clearly elucidated. Astrocytes pre-exposed to the CO-releasing compound CORM-2 increased mitochondrial biogenesis, mitochondrial electron transport components (cytochrome c, Cyt c; cytochrome c oxidase subunit 2, COX2), and ATP synthesis. The increased mitochondrial function was correlated with activation of AMP-activated protein kinase α and upregulation of HO-1, peroxisome proliferators-activated receptor γ-coactivator-1α (PGC-1α), and estrogen-related receptor α (ERRα). These events elicited by CORM-2 were suppressed by Ca2+ chelators, a HO inhibitor, and an L-type Ca2+ channel blocker, but not other Ca2+ channel inhibitors. Among the HO byproducts, combined CORM-2 and bilirubin treatment effectively increased PGC-1α, Cyt c and COX2 expression, mitochondrial biogenesis, and ATP synthesis, and these increases were blocked by Ca2+ chelators. Moreover, cerebral ischemia significantly increased HO-1, PGC-1α, and ERRα levels, subsequently increasing Cyt c and COX2 expression, in wild-type mice, compared with HO-1+/− mice. These results suggest that HO-1-derived CO enhances mitochondrial biogenesis in astrocytes by activating L-type Ca2+ channel-mediated PGC-1α/ERRα axis, leading to maintenance of astrocyte function and neuroprotection/recovery against damage of brain function.

Original languageEnglish
Pages (from-to)297-304
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2016 Oct 14

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) ( 2013M3A9B6046563 and 2016M3A9B6903103 ).

Publisher Copyright:
© 2016 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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