Cited by 57Mitochondrial Function and PathologyAutophagy in Disease and TherapyMetabolism, Diabetes, and Cancer

Decoding the Rosetta stone of mitonuclear communication

Open access
English, Justin, Son, Jyung Mean, Cardamone, Maria Dafne, Lee, Changhan, Perissi, Valentina·2020·Pharmacological Research

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.

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Crossref · 10.1016/j.phrs.2020.105161

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  • Metazoan mitonuclear signaling evolved independently and uses different mechanisms.

    “The human homolog of Rtg3p is the microphthalmia-associated transcription factor (MITF) (Goding and Arnheiter 2019), which is not involved in mitonuclear signaling that in Metazoa evolved independently and uses different mechanisms (Butow and Avadhani 2004; Jazwinski 2014; English et al. 2020).”

    From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as English et al. 2020

    The ‘Mitochondria-to-nucleus Signaling in Mammals’ section (page unavailable) says higher organisms use more complex communication strategies and a wider array of transcriptional regulators than the yeast RTG pathway, supporting the claim of different mechanisms. It also says overall goals and regulatory strategies are conserved across species; it does not establish that metazoan signaling evolved independently. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • MITF is not involved in mitonuclear signaling.

    “The human homolog of Rtg3p is the microphthalmia-associated transcription factor (MITF) (Goding and Arnheiter 2019), which is not involved in mitonuclear signaling that in Metazoa evolved independently and uses different mechanisms (Butow and Avadhani 2004; Jazwinski 2014; English et al. 2020).”

    From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as English et al. 2020

    The “Mitochondria-to-nucleus Signaling in Mammals” section describes mammalian regulators with functions similar to yeast Rtg1/Rtg3, but it does not say whether MITF participates in mitonuclear signaling. Searches for MITF and for the claimed evolutionary distinction found no passage establishing MITF’s exclusion. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
English, J., Son, J. M., Cardamone, M. D., Lee, C., & Perissi, V.
Affiliations
  • Boston University (US)
  • University of Southern California (US)
Corresponding author
Perissi, Valentina
Venue
Pharmacological Research
Publisher
Elsevier BV
Published
2020-11
Volume
161
Pages
105161
ISSN
1043-6618 (ISSN-L)
OpenAlex
W3081296598
Cited by
55
References
359
Citations by year
2026: 10 · 2025: 7 · 2024: 17 · 2023: 8 · 2022: 4 · 2021: 8 · 2020: 1
FWCI
0.50
Type
journal article
Language
en
Open access
Locations
  • Pharmacological Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (R01GM127625, 5T32GM008541)
  • VP, NIH (R01AG052258)
  • AFAR fellowship
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
mitochondria, nuclear genome, mitochondrial biogenesis, cellular homeostasis, mitochondrial pathway, mitochondrial metabolism, apoptosis, organelle evolution
MeSH terms
Animals, Cell Communication, Cell Nucleus, Gene Expression Regulation, Humans, Mitochondria, Nuclear Proteins, Signal Transduction, Mitochondrial Proteins

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