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Updated: Jun 1, 2026
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Protein kinase C epsilon affects mitochondrial function through estrogen-related receptor alpha
Na Lu1, Wenxian Wang, Jinsong Liu
1Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 190 Kai Yuan Avenue, Science Park, Guangzhou 510530, China.
Cellular Signalling
|May 21, 2011
Summary
Protein Kinase C (PKC) regulates mitochondrial function. Inhibiting PKCs alters mitochondrial mass, membrane potential, and reactive oxygen species, with PKCε specifically activating estrogen-related receptor α (ERRα).
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Signal Transduction
Background:
- Protein Kinase C (PKC) family members regulate critical cellular processes like proliferation, differentiation, and motility.
- These cellular functions are energy-intensive, necessitating a link between PKC signaling and cellular energy production.
- The precise mechanisms by which PKCs influence mitochondrial function and energy metabolism remain largely undefined.
Purpose of the Study:
- To investigate the role of Protein Kinase C (PKC) in regulating mitochondrial function and energy production.
- To elucidate the involvement of estrogen-related receptor α (ERRα) as a mediator in PKC-driven mitochondrial regulation.
- To identify specific PKC isoforms and ERRα residues critical for modulating mitochondrial homeostasis.
Main Methods:
- Utilized a broad-specificity PKC inhibitor (Gö6983) to assess the impact of PKC inhibition on mitochondrial parameters.
- Employed a PKC activator (phorbol ester, PMA) and an ERRα inverse agonist (XCT-790) to study signaling pathways.
- Over-expressed constitutively active PKC isoforms and performed site-directed mutagenesis on ERRα to pinpoint key interactions.
Main Results:
- PKC inhibition with Gö6983 reduced mitochondrial mass and altered mitochondrial function, increasing membrane potential (Δψm) and reactive oxygen species (ROS) levels.
- Gö6983 suppressed ERRα activity and the expression of its target genes (PPARα, MCAD), while PMA enhanced ERRα target gene PDK4 expression.
- PKCε was identified as a key isoform that enhances ERRα transcriptional activity, involving specific residues (Thr106, Ser110, Thr124) on ERRα.
Conclusions:
- Estrogen-related receptor α (ERRα) acts downstream of PKCε to regulate mitochondrial homeostasis.
- PKC signaling pathways significantly influence mitochondrial function and cellular energy metabolism.
- Targeting PKC-ERRα interactions may offer novel strategies for modulating mitochondrial health and energy production.
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