Next Article in Journal
Long Non-Coding RNA Profiling in a Non-Alcoholic Fatty Liver Disease Rodent Model: New Insight into Pathogenesis
Next Article in Special Issue
Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications
Previous Article in Journal
Comparative Solid-State Stability of Perindopril Active Substance vs. Pharmaceutical Formulation
Previous Article in Special Issue
The Emergence of the Dose–Response Concept in Biology and Medicine
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2017, 18(1), 165; doi:10.3390/ijms18010165

PERM Hypothesis: The Fundamental Machinery Able to Elucidate the Role of Xenobiotics and Hormesis in Cell Survival and Homeostasis

1
Department of Neurological and Movement Sciences, University of Verona, Verona 37134, Italy
2
Council for Nutritional and Environmental Medicine, Mo i Rana 8610, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Guido R.M.M. Haenen
Received: 29 October 2016 / Revised: 4 January 2017 / Accepted: 10 January 2017 / Published: 15 January 2017
(This article belongs to the Special Issue Hormesis and Transhormesis in Toxicology and Risk Assessment)
View Full-Text   |   Download PDF [2397 KB, uploaded 18 January 2017]   |  

Abstract

In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response. The “PERM hypothesis” suggests that xenobiotics can modulate this central signaling and the regulatory engine made fundamentally by the ER, mitochondria and proteasome, together with other ancillary components such as peroxisomes, by acting on the energetic balance, redox system and macromolecule turnover. In this context, reactive species and stressors are fundamentally signalling molecules that could act as negative-modulating signals if PERM-mediated control is offline, impaired or dysregulated, as occurs in metabolic syndrome, degenerative disorders, chronic inflammation and cancer. Calcium is an important oscillatory input of this regulation and, in this hypothesis, it might play a role in maintaining the correct rhythm of this PERM modulation, probably chaotic in its nature, and guiding cells to a more drastic decision, such as apoptosis. The commonest effort sustained by cells is to maintain their survival balance and the proterome has the fundamental task of supporting this mechanism. Mild stress is probably the main stimulus in this sense. Hormesis is therefore re-interpreted in the light of this hypothetical model and that experimental evidence arising from flavonoid and hormesis reasearch. View Full-Text
Keywords: mitochondria; proterome; reactive oxygen species (ROS); oxidative stress; flavonoids mitochondria; proterome; reactive oxygen species (ROS); oxidative stress; flavonoids
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Chirumbolo, S.; Bjørklund, G. PERM Hypothesis: The Fundamental Machinery Able to Elucidate the Role of Xenobiotics and Hormesis in Cell Survival and Homeostasis. Int. J. Mol. Sci. 2017, 18, 165.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top