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A new subset of mitochondrial-derived vesicles perform inter-mitochondrial communications

Priyanka Adla1, Vani Bshivakumar1, Dheeraj Pathak1

  • 1Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, TG 500046, India.

Molecular Biology of the Cell
|December 24, 2025
PubMed

Insights

Mitochondria form vesicles (MDVs) for cellular tasks. Researchers discovered a new subset of MDVs that communicate between mitochondria, revealing a novel cellular pathway.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Organelle Communication

Background:

  • Mitochondria utilize Mitochondrial-Derived Vesicles (MDVs) for cellular homeostasis, including protein transport and peroxisome regulation.
  • While MDV functions are expanding, known communication pathways are exclusively from mitochondria to other organelles.
  • The discovery of distinct MDV subsets highlights the complexity of mitochondrial intercellular signaling.

Purpose of the Study:

  • To investigate the generation and proteomic composition of in vitro generated MDVs from rat liver mitochondria.
  • To identify novel subsets of MDVs using live cell imaging in HepG2 cells.
  • To determine if MDVs can facilitate communication between mitochondria.

Main Methods:

  • Purification of mitochondria from rat liver for in vitro MDV generation.
  • Proteomic analysis of isolated MDVs to identify protein enrichment.
  • Live cell imaging studies in HepG2 cells using specific markers (TOMM70, TOMM20) to characterize MDV subsets.
  • Analysis of metabolic enzyme content within identified MDV subsets.

Main Results:

  • In vitro generated liver MDVs are enriched in metabolic proteins, reflecting the liver's metabolic role.
  • A novel subset of MDVs, positive for TOMM70 but negative for TOMM20, was identified in HepG2 cells.
  • This specific MDV subset contains metabolic enzymes like ALDH7A1.
  • These TOMM70+ve MDVs were observed to facilitate communication directly between mitochondria.

Conclusions:

  • Mitochondria-Derived Vesicles (MDVs) possess a previously unrecognized capacity for inter-mitochondrial communication.
  • A novel subset of MDVs, characterized by TOMM70 expression, plays a role in this newly discovered communication pathway.
  • This finding expands our understanding of mitochondrial function and intercellular signaling within the cell.

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