Mitochondrial proteases maintain cellular protein homeostasis and tissue integrity

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Mitochondrial proteases are crucial for protein import and quality control within mitochondria.
• Their broader physiological roles and impact on cytosolic proteostasis are not fully understood.

Purpose of the Study:

• To systematically investigate the in vivo functions of 15 conserved mitochondrial proteases.
• To explore their impact on mitochondrial and cytosolic proteostasis.

Main Methods:

• Generated loss- and gain-of-function alleles for 15 mitochondrial proteases in Drosophila melanogaster.
• Performed tissue-specific knockouts and analyzed phenotypes including protein aggregation, degeneration, and mitophagy.

Main Results:

• Disruption of proteases led to male sterility, lethality, mitochondrial aggregates, and age-dependent degeneration.
• Specific proteases influenced mitophagy and muscle integrity.
• Mitochondrial protease function, particularly Mppa and UQCR-C1, impacted aggregation and toxicity of polyglutamine proteins.

Conclusions:

• This research provides a comprehensive in vivo resource for understanding mitochondrial protease functions.
• It highlights their critical roles in both mitochondrial and cytosolic proteostasis, with implications for disease.