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Proteolytic coordination of the OXPHOS Life Cycle
Nataliia Nechytailo1,2, Karolina Szczepanowska1,3
1IMol, Polish Academy of Sciences, Flisa 6, 02-247 Warsaw, Poland.
The Biochemical Journal
|June 24, 2026
Summary
Mitochondrial proteases dynamically regulate the oxidative phosphorylation (OXPHOS) system, moving beyond simple quality control to actively shape energy production machinery. This review details how these proteases manage the entire OXPHOS life cycle.
Area of Science:
- Cellular Biology
- Biochemistry
- Mitochondrial Biology
Background:
- The mitochondrial oxidative phosphorylation (OXPHOS) system is vital for cellular energy production.
- Mitochondrial proteases were traditionally viewed as a simple quality-control mechanism.
- Recent proteomic advances reveal a complex network of proteases influencing OXPHOS.
Purpose of the Study:
- To review the multifaceted roles of mitochondrial proteases in regulating the OXPHOS system.
- To highlight how proteolysis actively shapes mitochondrial respiratory complexes.
- To summarize current understanding and emerging concepts in OXPHOS regulation by proteases.
Main Methods:
- Review of recent literature and proteomic findings.
- Analysis of proteolytic circuits associated with OXPHOS.
- Synthesis of data on protease functions in OXPHOS regulation.
Main Results:
- Mitochondrial proteases form a coordinated network actively shaping OXPHOS machinery.
- Specialized proteases have distinct functions in managing OXPHOS complexes.
- Proteolysis regulates OXPHOS expression, assembly, maintenance, and disposal.
Conclusions:
- Mitochondrial proteases are key regulators of the OXPHOS life cycle.
- Emerging concepts include asynchronous turnover, cofactor-driven proteolysis, and bioenergetics-coupled degradation.
- Further research will deepen understanding of protease coordination in OXPHOS regulation.
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