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Review
. 2020 Nov:161:105161.
doi: 10.1016/j.phrs.2020.105161. Epub 2020 Aug 23.

Decoding the rosetta stone of mitonuclear communication

Justin English  1 , Jyung Mean Son  2 , Maria Dafne Cardamone  3 , Changhan Lee  4 , Valentina Perissi  5
Affiliations
Review

Decoding the rosetta stone of mitonuclear communication

Justin English et al. Pharmacol Res. 2020 Nov.

Abstract

Cellular homeostasis in eukaryotic cells requires synchronized coordination of multiple organelles. A key role in this stage is played by mitochondria, which have recently emerged as highly interconnected and multifunctional hubs that process and coordinate diverse cellular functions. Beyond producing ATP, mitochondria generate key metabolites and are central to apoptotic and metabolic signaling pathways. Because most mitochondrial proteins are encoded in the nuclear genome, the biogenesis of new mitochondria and the maintenance of mitochondrial functions and flexibility critically depend upon effective mitonuclear communication. This review addresses the complex network of signaling molecules and pathways allowing mitochondria-nuclear communication and coordinated regulation of their independent but interconnected genomes, and discusses the extent to which dynamic communication between the two organelles has evolved for mutual benefit and for the overall maintenance of cellular and organismal fitness.

Keywords: Acetyl-Coenzyme A (PubChem CID: 6302); Alpha-ketoglutarate (PubChem CID: 164533); Antimycin (PubChem CID: 12550); Carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubChem CID: 2603); Communication; Epigenetics; Humanin (PubChem CID: 16131438); Integrated stress response; Mitochondrial retrograde signaling; Mitonuclear; Nicotinamide riboside (PubChem CID: 439924); Oligoymycin (PubChem CID: 78358496); S-adenosylmethionine (SAM) (PubChem CID: 34756); Superoxide anion (PubChem CID: 5359597).

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Conflict of interest statement

Declaration of interest: C.L. is a consultant and shareholder of CohBar, Inc.

Figures

Figure 1.
Figure 1.
Mitochondrial-derived signaling molecules promoting mitonuclear communication. Mitochondria-derived signaling molecules promote signaling to the nucleus through both direct and indirect actions. They can be classified in three broad categories as discussed in the text: 1)Peptides, 2)mtDNA, and 3)Small molecules & Metabolites such as ROS, NAD+, Ca+, Acetyl-CoA, α-KG, 2-HG, succinate, fumarate.
Figure 2.
Figure 2.
Mitochondria stress response (MSR) and remodeling on nuclear chromatin via histone methylation and demethylation. Chromatin remodeling through methylation/demethylation of histone tails supports the reprogramming of nuclear gene expression in response to mitochondria dysfunctions across species. In the top panel, it is outlined the mtUPR arm of the MSR in C. elegans. Nuclear translocation of transcription factors ATFS-1 and DVE-1 promotes the expression of stress response genes that are excluded from chromatin condensation mediated by H3K9 methyltransferase MET-2 and nuclear cofactor LIN-65. Accessibility of stress responsive promoters is guaranteed by the action of histone H3K9 and H3K27 demethylases, respectively KDM4A or jMJD1.2/PHF8 and JMJD3.1/JMJD3 as shown in mammals in the bottom panel. Mitochondria-to-nucleus translocation of GPS2, upon mitochondrial stress-induced de-sumoylation by SENP1, promotes demethylation of target promoters by stabilizing KDM4A through inhibition of Ubc13-dependent ubiquitination.
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References

    1. Abate M, Festa A, Falco M, Lombardi A, Luce A, Grimaldi A, Zappavigna S, Sperlongano P, Irace C, Caraglia M and Misso G (2020) Mitochondria as playmakers of apoptosis, autophagy and senescence. Semin Cell Dev Biol 98:139–153. - PubMed
    1. Adams KL and Palmer JD (2003) Evolution of mitochondrial gene content: gene loss and transfer to the nucleus. Mol Phylogenet Evol 29:380–395. - PubMed
    1. Al-Mehdi AB, Pastukh VM, Swiger BM, Reed DJ, Patel MR, Bardwell GC, Pastukh VV, Alexeyev MF and Gillespie MN (2012) Perinuclear mitochondrial clustering creates an oxidant-rich nuclear domain required for hypoxia-induced transcription. Science signaling 5:ra47. - PMC - PubMed
    1. Allis CD and Jenuwein T (2016) The molecular hallmarks of epigenetic control. Nature reviews Genetics 17:487–500. - PubMed
    1. Alves-Fernandes DK and Jasiulionis MG (2019) The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer. International journal of molecular sciences 20. - PMC - PubMed

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