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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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
Volume479
Issue number2
DOIs
Publication statusPublished - 2016 Oct 14

Fingerprint

Heme Oxygenase-1
Organelle Biogenesis
Carbon Monoxide
Heme Oxygenase (Decyclizing)
Chemical activation
Astrocytes
Chelating Agents
Adenosine Triphosphate
Peroxisome Proliferator-Activated Receptors
AMP-Activated Protein Kinases
Cytoprotection
Recovery of Function
Electron Transport Complex IV
Electron Transport
Cytochromes c
Brain Ischemia
Bilirubin
Energy Metabolism
Byproducts
Brain

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Choi, Yoon Kyung ; Park, Joon Ha ; Baek, Yi Yong ; Won, Moo Ho ; Jeoung, Dooil ; Lee, Hansoo ; Ha, Kwon Soo ; Kwon, Young-Guen ; Kim, Young Myeong. / Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca2+ channel-mediated PGC-1α/ERRα activation. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 479, No. 2. pp. 297-304.
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Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca2+ channel-mediated PGC-1α/ERRα activation. / Choi, Yoon Kyung; Park, Joon Ha; Baek, Yi Yong; Won, Moo Ho; Jeoung, Dooil; Lee, Hansoo; Ha, Kwon Soo; Kwon, Young-Guen; Kim, Young Myeong.

In: Biochemical and Biophysical Research Communications, Vol. 479, No. 2, 14.10.2016, p. 297-304.

Research output: Contribution to journalArticle

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T1 - Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca2+ channel-mediated PGC-1α/ERRα activation

AU - Choi, Yoon Kyung

AU - Park, Joon Ha

AU - Baek, Yi Yong

AU - Won, Moo Ho

AU - Jeoung, Dooil

AU - Lee, Hansoo

AU - Ha, Kwon Soo

AU - Kwon, Young-Guen

AU - Kim, Young Myeong

PY - 2016/10/14

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N2 - 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.

AB - 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.

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