Complex folded proteins are processed by the ER which is the likely target of spermidine. The ER is adjacent and joined to mitochondria by the MAM mitochondrial membrane. A common membrane allows intimate and targeted exchange of compounds for mutual and symbiotic benefit. "I'll scratch your back if you'll scratch mine."
I suspect that enzymes critical for transport of fuel substrates into mitochondria (and their subsequent conversion into ATP energy) are produced by ER. Therefore oxidative stress, in the absence of spermidine, impedes the efficiency of mitochondria, a hallmark of aging that would not compensate with larger numbers of mitochondria that would come at a cost of even greater oxidative stress.
Only fasting, autophagy, sulforaphane induced greater endogenous antioxidants production and increased spermidine improved proteostasis that works via greater autophagy and reduced mitochondrial/ER oxidative stress would restore efficiency and normalize the increased oxidative stress of aging.
The Endoplasmic Reticulum: A Hub of Protein Quality Control in Health and Disease
Review article
- Lisa Vincenz-Donnelly
- Mark S. Hipp
Abstract
One third of the eukaryotic proteome is synthesized at the endoplasmic reticulum (ER), whose unique properties provide a folding environment substantially different from the cytosol. A healthy, balanced proteome in the ER is maintained by a network of factors referred to as the ER quality control (ERQC) machinery. This network consists of various protein folding chaperones and modifying enzymes, and is regulated by stress response pathways that prevent the build-up as well as the secretion of potentially toxic and aggregation-prone misfolded protein species. Here, we describe the components of the ERQC machinery, investigate their response to different forms of stress, and discuss the consequences of ERQC break-down.
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