Mitochondrial MicroRNAs Contribute to Macrophage Immune Functions Including Differentiation, Polarization, and Activation.

Autor:	Duroux-Richard I; IRMB, INSERM, Université de Montpellier, CHU Montpellier, Montpellier, France., Apparailly F; IRMB, INSERM, Université de Montpellier, CHU Montpellier, Montpellier, France.; Clinical Department for Osteoarticular Diseases, University Hospital of Montpellier, Montpellier, France., Khoury M; Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.; Cells for Cells and REGENERO, The Chilean Consortium for Regenerative Medicine, Santiago, Chile.; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2021 Nov 03; Vol. 12, pp. 738140. Date of Electronic Publication: 2021 Nov 03 (Print Publication: 2021).
DOI:	10.3389/fphys.2021.738140
Abstrakt:	A subset of microRNA (miRNA) has been shown to play an important role in mitochondrial (mt) functions and are named MitomiR. They are present within or associated with mitochondria. Most of the mitochondrial miRNAs originate from the nucleus, while a very limited number is encoded by mtDNA. Moreover, the miRNA machinery including the Dicer and Argonaute has also been detected within mitochondria. Recent, literature has established a close relationship between miRNAs and inflammation. Indeed, specific miRNA signatures are associated with macrophage differentiation, polarization and functions. Nevertheless, the regulation of macrophage inflammatory pathways governed specifically by MitomiR and their implication in immune-mediated inflammatory disorders remain poorly studied. Here, we propose a hypothesis in which MitomiR play a key role in triggering macrophage differentiation and modulating their downstream activation and immune functions. We sustain this proposition by bioinformatic data obtained from either the human monocytic THP1 cell line or the purified mitochondrial fraction of PMA-induced human macrophages. Interestingly, 22% of the 754 assayed miRNAs were detected in the mitochondrial fraction and are either exclusively or highly enriched cellular miRNA. Furthermore, the in silico analysis performed in this study, identified a specific MitomiR signature associated with macrophage differentiation that was correlated with gene targets within the mitochondria genome or with mitochondrial pathways. Overall, our hypothesis and data suggest a previously unrecognized link between MitomiR and macrophage function and fate. We also suggest that the MitomiR-dependent control could be further enhanced through the transfer of mitochondria from donor to target cells, as a new strategy for MitomiR delivery. Competing Interests: MK was the chief scientific officer of Cells for Cells and Regenero, the Chilean Consortium for Regenerative Medicine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Duroux-Richard, Apparailly and Khoury.)
Databáze:	MEDLINE
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