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Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays
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Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays

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Vps13-Mcp1 interact at vacuole-mitochondria interfaces and bypass ER-mitochondria contact sites

Arun T John Peter1, Beatrice Herrmann1, Diana Antunes2

  • 1ETH Zürich, Institute of Biochemistry, Zürich, Switzerland.

The Journal of Cell Biology
|September 3, 2017
PubMed

Insights

Mitochondrial protein Mcp1 recruits Vps13 to vacuole-mitochondria contacts, bypassing defects in endoplasmic reticulum-mitochondria encounter structure (ERMES) complexes. This pathway compensates for lost ERMES function, maintaining mitochondrial homeostasis.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Membrane Biology

Background:

  • Membrane contact sites (MCS) between the endoplasmic reticulum (ER) and mitochondria, facilitated by the ER-mitochondria encounter structure (ERMES) complex, are vital for cellular functions.
  • Disruptions in ERMES can be compensated by specific mutations or protein overexpressions, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the bypass mechanism for ERMES defects involving the endosomal protein Vps13 and the mitochondrial protein Mcp1.
  • To define the roles of Mcp1 and Vps13 in maintaining mitochondrial homeostasis when ERMES function is compromised.

Main Methods:

  • Investigated the interaction and functional relationship between Mcp1 and Vps13 using cellular and molecular biology techniques.
  • Analyzed the localization and recruitment of Vps13 to mitochondria in the presence and absence of functional ERMES.
  • Examined the role of Mcp1 in mediating vacuole-mitochondria contacts and compensating for ERMES loss.

Main Results:

  • Mitochondrial outer membrane protein Mcp1 actively recruits the endosomal protein Vps13 to mitochondria.
  • Mcp1 promotes the association of Vps13 with vacuole-mitochondria contact sites.
  • Vps13 and Mcp1 function together as effectors at vacuole-mitochondria contacts, compensating for the absence of ERMES-mediated ER-mitochondria contacts.

Conclusions:

  • Mcp1 and Vps13 act as key functional components at vacuole-mitochondria contact sites, independent of ERMES.
  • These proteins establish alternative contact sites that maintain mitochondrial homeostasis when ERMES is impaired.
  • The findings reveal a novel compensatory pathway for ERMES dysfunction crucial for cell survival and mitochondrial health.

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