Human cellular mitochondrial remodelling is governed by miR-2909 RNomics

Area of Science:

• Cell Biology
• Molecular Biology
• Epigenetics

Background:

• Mitochondrial remodeling via aerobic glycolysis is known to revert somatic cells to a stem-like phenotype.
• This study investigates the role of miR-2909 in reprogramming human peripheral blood mononuclear cells (PBMCs).

Purpose of the Study:

• To demonstrate miR-2909's capacity to reprogram PBMCs towards mitochondrial remodeling and aerobic glycolysis.
• To investigate if reprogrammed PBMCs exhibit stem-like characteristics, including intracellular lipid inclusions and survival gene expression.

Main Methods:

• Human PBMCs were engineered to ectopically express miR-2909.
• Gene expression analysis (RT-qPCR) of key stemness, metabolic, and survival markers was performed.
• Cellular ultrastructure was examined using transmission electron microscopy and morphometric analysis.

Main Results:

• Ectopic miR-2909 expression induced a stem-like phenotype in PBMCs, characterized by altered mitochondrial morphology (globular, cristae-poor).
• Compromised mitochondrial function was confirmed through various assays, including ATP levels, GSSG/GSH ratio, and cytochrome c oxidase activity.
• Increased lactate secretion and altered lipid metabolism were observed, consistent with aerobic glycolysis.

Conclusions:

• The results suggest that miR-2909 can reprogram PBMCs into a de-differentiated, stem-like state.
• miR-2909, encoded by the AATF gene, is proposed to function as an epigenetic switch driving aerobic glycolysis for de-differentiation.