Bibliographic Details
Title: |
Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins |
Authors: |
Michael A. Cahill |
Source: |
Frontiers in Bioscience-Landmark, Vol 27, Iss 11, p 317 (2022) |
Publisher Information: |
IMR Press, 2022. |
Publication Year: |
2022 |
Collection: |
LCC:Biochemistry LCC:Biology (General) |
Subject Terms: |
steroid biology, eukaryogenesis, membrane-associated progesterone receptor, neurogenesis, neurobiology, synapse, cyp51a1, candidate phyla radiation bacteria, heme, redox, metabolism, translational control, eumetazoa, eumetazoans, leumca, gastrulation, gastrulation organizer, blastoporal axial organizer, pluripotent stem cells, tmem97, sigma-2 receptor, cell motility, sleep, epigenetics, aging, aging clock, tyrosine phosphorylation, epithelial-mesenchymal transition, emt, Biochemistry, QD415-436, Biology (General), QH301-705.5 |
More Details: |
The title usage of Unde venisti ‘from where have you come’ is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influence modern human biology: via a formative trajectory from an evolutionarily foundational fulcrum. There is an arguable probability, although not a certainty, that PGRMC-like proteins were involved in eukaryogenesis. If so, then the proto-eukaryotic ancestral protein is modelled as having initiated the oxygen-induced and CYP450 (Cytochrome P450)-mediated synthesis of sterols in the endoplasmic reticulum to regulate proto-mitochondrial activity and heme homeostasis, as well as having enabled sterol transport between endoplasmic reticulum (ER) and mitochondria membranes involving the actin cytoskeleton, transport of heme from mitochondria, and possibly the regulation/origins of mitosis/meiosis. Later, during animal evolution, the last eumetazoan common ancestor (LEUMCA) acquired PGRMC phosphorylated tyrosines coincidentally with the gastrulation organizer, Netrin/deleted in colorectal carcinoma (DCC) signaling, muscle fibers, synapsed neurons, and neural recovery via a sleep-like process. Modern PGRMC proteins regulate multiple functions, including CYP450-mediated steroidogenesis, membrane trafficking, heme homeostasis, glycolysis/Warburg effect, fatty acid metabolism, mitochondrial regulation, and genomic CpG epigenetic regulation of gene expression. The latter imposes the system of differentiation status-sensitive cell-type specific proteomic complements in multi-tissued descendants of the LEUMCA. This paper attempts to trace PGRMC functions through time, proposing that key functions were involved in early eukaryotes, and were later added upon in the LEUMCA. An accompanying paper considers the implications of this awareness for human health and disease. |
Document Type: |
article |
File Description: |
electronic resource |
Language: |
English |
ISSN: |
2768-6701 |
Relation: |
https://www.imrpress.com/journal/FBL/27/11/10.31083/j.fbl2711317; https://doaj.org/toc/2768-6701 |
DOI: |
10.31083/j.fbl2711317 |
Access URL: |
https://doaj.org/article/5145fbc18e6e4a12be1c8463c298ada9 |
Accession Number: |
edsdoj.5145fbc18e6e4a12be1c8463c298ada9 |
Database: |
Directory of Open Access Journals |