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Melatonin reshapes the mitochondrial network and promotes intercellular mitochondrial transfer via tunneling nanotubes after ischemic‐like injury in hippocampal HT22 cells
Author(s) -
Nasoni Maria Gemma,
Carloni Silvia,
Caico Barbara,
Burattini Sabrina,
Cesarini Erica,
Papa Stefano,
Pagliarini Marica,
Ambrogini Patrizia,
Balduini Walter,
Luchetti Francesca
Publication year - 2021
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12747
Subject(s) - mfn2 , melatonin , microbiology and biotechnology , mitochondrial fusion , mitochondrion , mitochondrial fission , fis1 , dnm1l , viability assay , reactive oxygen species , mfn1 , pink1 , biology , mitochondrial biogenesis , chemistry , mitochondrial dna , cell , biochemistry , apoptosis , mitophagy , endocrinology , autophagy , gene
Abstract Mitochondrial dysfunction is considered one of the hallmarks of ischemia/reperfusion injury. Mitochondria are plastic organelles that undergo continuous biogenesis, fusion, and fission. They can be transferred between cells through tunneling nanotubes (TNTs), dynamic structures that allow the exchange of proteins, soluble molecules, and organelles. Maintaining mitochondrial dynamics is crucial to cell function and survival. The present study aimed to assess the effects of melatonin on mitochondrial dynamics, TNT formation, and mitochondria transfer in HT22 cells exposed to oxygen/glucose deprivation followed by reoxygenation (OGD/R). The results showed that melatonin treatment during the reoxygenation phase reduced mitochondrial reactive oxygen species (ROS) production, improved cell viability, and increased the expression of PGC1α and SIRT3. Melatonin also preserved the expression of the membrane translocase proteins TOM20 and TIM23, and of the matrix protein HSP60, which are involved in mitochondrial biogenesis. Moreover, it promoted mitochondrial fusion and enhanced the expression of MFN2 and OPA1. Remarkably, melatonin also fostered mitochondrial transfer between injured HT22 cells through TNT connections. These results provide new insights into the effect of melatonin on mitochondrial network reshaping and cell survival. Fostering TNTs formation represents a novel mechanism mediating the protective effect of melatonin in ischemia/reperfusion injury.