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. 2021 Apr 6;12(4):358. doi: 10.1038/s41419-021-03640-9

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Mitochondria play greatly important roles in generating ATP through oxidative phosphorylation (OXPHOS). The main mitochondrial-dependent signaling events: the release of mitochondrial ROS to induce the changes of gene expression through HIF/AMPK/Ca²⁺/Cn; release of metabolites to induce histone acetylation, histone and DNA demethylation, which determined cell differentiation; activation of AMPK regulates mitochondrial metabolism, mitophagy, and mitochondrial fission and fusion; release of cytochrome C activates caspases cascade reaction to induce cell death; release of mtDNA causes the secretion of pro-inflammatory cytokines. Moreover, mitochondrial outer membrane (MOM) can be used as a signaling platform. B cell lymphoma-2 (BCL-2)-associated X protein (BAX) and BCL-2 antagonist/killer 1 (BAK), endoplasmic reticulum (ER), Ca2+/ Calcineurin (Cn), hypoxia inducible factor (HIF), Adenosine monophosphate‑activated protein kinase (AMPK).