Related Experiment Video
Updated: Feb 3, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
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.
Abstract:
During senescence, cells undergo distinctive biochemical and morphological changes and become dysfunctional. MiRNAs are involved in the senescence process and specific miRNAs can localize to mitochondria (mitomiRs). We hypothesized that part of the typical alterations of senescence may depends on mitomiRs deregulation. Therefore, we thoroughly explored the phenotype of human endothelial cells undergoing replicative senescence (sHUVECs) and observed elongated/branched mitochondria, accumulation of autophagic vacuoles (AVs), increased ROS and IL-1β production and reduced expression of Bcl-2 compared to younger cells (yHUVECs). Despite these pro-apoptotic features, sHUVECs are more resistant to serum deprivation, conceivably due to development of pro-survival strategies such as upregulation of Bcl-xL and Survivin. We demonstrate that mitomiR-181a, -34a, and -146a, are overexpressed and localize to mitochondria in sHUVECs compared with yHUVECs and that they: i) down-regulate Bcl-2, ii) induce permeability transition pore opening and activation of caspase-1 and 3, iii) affect sensitivity to apoptosis and iv) promote the conversion of LC3-I to LC3-II. Overall, we document for the first time that some mitomiRs can act as mediators of the multiple but functionally linked biochemical and morphological changes that characterize aging cells and that they can promote different cellular outcomes according to the senescence status of the cell.
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.
Related Concept Videos
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Replicative Cell Senescence
Animal Mitochondrial Genetics
Hypothalamic-Pituitary Axis
Export of Mitochondrial and Chloroplast Genes
Functional Brain Systems: Reticular Formation
Within the reticular formation, there are several distinct nuclei that can be classified into three broad categories. The Raphe nuclei are located along the midline of the brainstem. They are primarily known for their role in synthesizing and releasing serotonin, a neurotransmitter involved in regulating mood, appetite, sleep, and circadian rhythms. The...

