Disturbance in communication between mitochondrial redox processes and the AMPK/PGC-1α/SIRT-1 axis influences diverse
Akhil Akhil1, Rohit Bansal1, Ankita Ankita1
1Department of Biochemistry, BMS-Block II, South Campus, Panjab University, Chandigarh 160014 India.
Background:
Mechanisms behind multiple organ involvement in lupus, is still an enigma for researchers. Mitochondrial dysfunction and oxidative stress are known to be important aspects in lupus etiology however, their role in lupus organ manifestation is yet to be understood. The present study is based on the understanding of interplay between AMPK/PGC-1α/SIRT-1 axis, mitochondrial complexes, and anti-oxidants levels, which might be involved in lupus organ pathology.
Methodology:
Pristane-induced Balb/c mice lupus model (PIL) was utilised and evaluation of anti-oxidants, mitochondrial complexes, pro-inflammatory cytokines levels, biochemical parameters were performed by standard procedures. Tissues were studied by haematoxylin and eosin staining followed by immunohistochemistry. The AMPK/PGC-1α/SIRT-1 expression was analysed by using qPCR and flowcytometry. Analysis of reactive oxygen species (ROS) among WBCs was performed by using various dyes (DCFDA, Mitosox, JC-1) on flowcytometry.
Result:
Significant presence of immune complexes (Tissue sections), ANA (Serum), and pro-inflammatory cytokines (plasma), diminished anti-oxidants and altered biochemical parameters depict the altered pathology in PIL which was accompanied by dysregulated mitochondrial complex activity. Differential expression of the AMPK/PGC-1α/SIRT-1 axis was detected in tissue and correlation with mitochondrial and antioxidant activity emerged as negative in PIL group while positive in controls. Close association was observed between ROS, mitochondrial membrane potential, and AMPK/PGC-1α/SIRT-1 axis in WBCs.
Conclusion:
This study concludes that mitochondria play a dual role in lupus organ pathology, contributing to organ damage while also potentially protecting against damage through the regulation of interactions between antioxidants and the AMPK axis expression.
Insights
Mitochondria play a dual role in lupus organ pathology, potentially causing damage and offering protection. This involves regulating interactions between antioxidants and the AMPK signaling pathway.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Mechanisms of multiple organ involvement in lupus remain unclear.
- Mitochondrial dysfunction and oxidative stress are implicated in lupus etiology but their role in organ manifestation is not fully understood.
- This study investigates the interplay between the AMPK/PGC-1α/SIRT-1 axis, mitochondrial complexes, and antioxidant levels in lupus organ pathology.
Purpose of the Study:
- To elucidate the role of mitochondrial dysfunction and oxidative stress in lupus organ pathology.
- To explore the relationship between the AMPK/PGC-1α/SIRT-1 axis, mitochondrial function, and antioxidant status in a lupus model.
- To understand the dual role of mitochondria in lupus-related organ damage and protection.
Main Methods:
- Utilized a pristane-induced lupus (PIL) mouse model.
- Assessed antioxidants, mitochondrial complexes, pro-inflammatory cytokines, and biochemical parameters.
- Analyzed AMPK/PGC-1α/SIRT-1 expression via qPCR and flow cytometry; quantified reactive oxygen species (ROS) in white blood cells (WBCs).
Main Results:
- PIL mice exhibited immune complexes, antinuclear antibodies (ANA), elevated cytokines, diminished antioxidants, and altered biochemical parameters with dysregulated mitochondrial activity.
- The AMPK/PGC-1α/SIRT-1 axis showed differential expression, negatively correlating with mitochondrial and antioxidant activity in PIL mice.
- A strong association was found between ROS, mitochondrial membrane potential, and the AMPK/PGC-1α/SIRT-1 axis in WBCs.
Conclusions:
- Mitochondria exert a dual role in lupus organ pathology, contributing to damage and offering protection.
- Mitochondrial protection is mediated through regulating interactions between antioxidants and AMPK axis expression.
- Findings highlight mitochondria as a potential therapeutic target in lupus management.
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