Decoding the Rosetta stone of mitonuclear communication
Open accessAbstract
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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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 measuredMITF 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)
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Mitochondrial-to-nuclear communication in aging: an epigenetic perspective
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Cnm1 mediates nucleus–mitochondria contact site formation in response to phospholipid levels
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Harnessing Mitochondrial Stress for Health and Disease: Opportunities and Challenges
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Mitonuclear Communication in Stem Cell Function
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Organelle Communication: Joined in Sickness and in Health
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Synthesis of a novel mitochondrial fluorescent probe - killing cancer cells in vitro and in vivo
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Inhibition of Mul1-mediated ubiquitination promotes mitochondria-associated translationPreprint
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Mitochondria Dictate Progressive Versus Bimodal Aging of the Mammary Gland
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From endosymbiont to signalling hub: evolution and functional integration of mitochondria
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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)
- PMC
- PMC7755734
- 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
- green
- europepmc.org
- 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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