The mitomiR/Bcl-2 axis affects mitochondrial function and autophagic vacuole formation in senescent endothelial cells

Angelica Giuliani1, Ilenia Cirilli2, Francesco Prattichizzo3

  • 1Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy.

Aging
|October 24, 2018
PubMed

Insights

Mitochondrial microRNAs (mitomiRs) contribute to cellular aging by altering cell function and survival pathways. These aging-associated mitomiRs regulate apoptosis and autophagy, impacting cellular outcomes during senescence.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Aging Research

Background:

  • Cellular senescence involves significant biochemical and morphological changes, leading to cellular dysfunction.
  • MicroRNAs (miRNAs) play a role in senescence, with some localizing to mitochondria (mitomiRs).

Purpose of the Study:

  • To investigate the role of deregulated mitomiRs in the cellular alterations associated with replicative senescence.
  • To explore the impact of specific mitomiRs on mitochondrial function, apoptosis, and autophagy in senescent human endothelial cells.

Main Methods:

  • Phenotypic analysis of senescent human umbilical vein endothelial cells (sHUVECs) compared to young cells (yHUVECs).
  • Mitochondrial localization and expression analysis of specific mitomiRs (miR-181a, -34a, -146a).
  • Assessment of apoptosis-related proteins (Bcl-2, Bcl-xL, Survivin, caspases), reactive oxygen species (ROS), IL-1β, and autophagy markers (LC3).

Main Results:

  • Senescent cells exhibited elongated mitochondria, increased ROS and IL-1β, and altered apoptosis/autophagy markers.
  • Overexpressed mitomiRs (miR-181a, -34a, -146a) were found in mitochondria of sHUVECs.
  • These mitomiRs downregulated Bcl-2, induced mitochondrial permeability transition pore opening, activated caspases, and promoted LC3-II conversion.

Conclusions:

  • Specific mitomiRs act as mediators of senescence-associated cellular changes.
  • MitomiRs contribute to both pro-apoptotic and pro-survival signaling pathways during cellular aging.
  • MitomiRs influence cellular outcomes by modulating apoptosis and autophagy in senescent cells.

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