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Presequence-dependent folding ensures MrpL32 processing by the m-AAA protease in mitochondria

Florian Bonn1, Takashi Tatsuta, Carmelina Petrungaro

  • 1Institute for Genetics, Center for Molecular Medicine (CMMC), Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

The EMBO Journal
|May 26, 2011
PubMed

Insights

Mitochondrial proteases decide whether to process or degrade proteins. Protein folding, influenced by mitochondrial targeting, determines MrpL32 maturation, impacting neurodegeneration.

Area of Science:

  • Mitochondrial biology
  • Protein processing
  • Neurodegenerative disease

Background:

  • Mitochondrial AAA proteases (m-AAA) perform dual roles: protein processing and quality control.
  • Dysfunction of m-AAA proteases is linked to neurodegeneration.
  • The mechanism dictating m-AAA protease substrate fate (processing vs. degradation) remains unclear.

Purpose of the Study:

  • To elucidate how m-AAA proteases differentiate between specific protein processing and complete degradation.
  • To investigate the role of protein folding and mitochondrial targeting in m-AAA protease substrate selection.
  • To understand the regulation of ribosomal protein MrpL32 maturation and its implications.

Main Methods:

  • Investigated the processing and degradation of ribosomal protein MrpL32 by m-AAA proteases.
  • Analyzed the role of a conserved CxxC-X(9)-CxxC motif in MrpL32 folding and maturation.
  • Examined the impact of oxidative stress and mitochondrial targeting sequences on MrpL32 fate.

Main Results:

  • Formation of a folded domain in MrpL32, mediated by a CxxC-X(9)-CxxC motif, halts N-terminal degradation and releases mature MrpL32.
  • Oxidative stress disrupts MrpL32 folding, leading to its degradation by m-AAA proteases and reduced mitochondrial translation.
  • Mitochondrial targeting sequence is crucial for MrpL32 folding, necessitating post-translational processing by m-AAA proteases.

Conclusions:

  • Mitochondrial protein folding, guided by targeting sequences, dictates substrate selection by m-AAA proteases.
  • Maturational processing of MrpL32 by m-AAA proteases is essential for ribosome biogenesis and mitochondrial function.
  • Impaired folding and subsequent degradation of MrpL32 under oxidative stress may contribute to neurodegenerative processes.

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