Mitochondrial-derived compartments remove surplus proteins from the outer mitochondrial membrane

Zachary N Wilson1, Sai Sangeetha Balasubramaniam1, Sara Wong1

  • 1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.

PubMed

Insights

Mitochondrial-derived compartments (MDCs) sequester excess outer mitochondrial membrane proteins. This mechanism helps maintain mitochondrial integrity by trapping aberrant proteins on the mitochondrial surface.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Protein Homeostasis

Background:

  • The outer mitochondrial membrane (OMM) regulates protein import and removal of damaged proteins.
  • The mechanism by which the OMM senses and removes aberrant proteins is not fully understood.
  • Mitochondrial-derived compartments (MDCs) were previously identified as a mechanism for removing mitochondrial proteins.

Purpose of the Study:

  • To investigate how the OMM senses aberrant proteins and maintains its integrity.
  • To elucidate the role of MDCs in managing the OMM proteome.
  • To understand the selective sorting of proteins into MDCs.

Main Methods:

  • Investigated protein localization and sequestration within MDCs.
  • Analyzed the role of the translocase of the outer membrane (TOM) complex assembly in MDC formation.
  • Studied the effects of excess mitochondrial membrane proteins and mistargeted proteins on MDC formation.

Main Results:

  • MDCs specifically sequester proteins localized to the OMM.
  • Subunits of the TOM complex are excluded from MDCs unless TOM assembly is impaired.
  • Overloading the OMM with proteins induces MDC formation and sequestration.

Conclusions:

  • MDCs selectively trap OMM-localized proteins.
  • MDCs play a role in maintaining OMM integrity by sequestering excess or aberrant proteins.
  • MDCs function as an OMM-enriched trap to segregate proteins from the mitochondrial surface.

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