Mito-Nuclear Communication by Mitochondrial Metabolites and Its Regulation by B-Vitamins

Abstract

Mitochondria are cellular organelles that control metabolic homeostasis and ATP generation, but also play an important role in other processes, like cell death decisions and immune signaling. Mitochondria produce a diverse array of metabolites that act in the mitochondria itself, but also function as signaling molecules to other parts of the cell. Communication of mitochondria with the nucleus by metabolites that are produced by the mitochondria provides the cells with a dynamic regulatory system that is able to respond to changing metabolic conditions. Dysregulation of the interplay between mitochondrial metabolites and the nucleus has been shown to play a role in disease etiology, such as cancer and type II diabetes. Multiple recent studies emphasize the crucial role of nutritional cofactors in regulating these metabolic networks. Since B-vitamins directly regulate mitochondrial metabolism, understanding the role of B-vitamins in mito-nuclear communication is relevant for therapeutic applications and optimal dietary lifestyle. In this review, we will highlight emerging concepts in mito-nuclear communication and will describe the role of B-vitamins in mitochondrial metabolite-mediated nuclear signaling.

X-ray tomography of cryopreserved human prostate cancer cells: mitochondrial targeting by an organoiridium photosensitiser

“…On the contrary, heavily altered smaller mitochondria, and severe membrane blebbing, indicating initiation of a celldeath process [48], were visible when cells were treated with 1 μM 1 and irradiated with blue light (Figs. 2b and 3d, Fig.…”

Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the I Q site of mitochondrial complex I

“…The result was similar for all three inhibitors (Figure C‐D). Over time, this would probably result in an accumulation of Krebs cycle intermediates, which have signaling effect for the rebuilding of the metabolism . The stress test conducted in the absence and presence of PQS, HQNO, and Rotenone revealed a strong and comparable inhibitory effect on the mitochondrial respiration under non‐inhibited, uncoupled, and inhibited conditions.…”

“…Over time, this would probably result in an accumulation of Krebs cycle intermediates, which have signaling effect for the rebuilding of the metabolism. 15 The stress test conducted in the absence and presence of PQS, HQNO, and Rotenone revealed a strong and comparable inhibitory effect on the mitochondrial respiration under non-inhibited, uncoupled, and inhibited conditions. Acute treatment with 10 µmol/L PQS resulted in significant reduction in respiration, including basal, spare respiratory capacity, as well as complex V linked respiration in both cell lines (Figure 2E-F).…”

“…For example, PQS was demonstrated to repress growth of other bacteria, likely by an iron‐chelating activity . A reduction in oxygen consumption was also observed . Effects on eukaryotic hosts include immunomodulatory activities .…”

“…[12][13][14] A reduction in oxygen consumption was also observed. 15 Effects on eukaryotic hosts include immunomodulatory activities. 16,17 In clinical samples of CF patients, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), another AQ type molecule produced by P aeruginosa, was identified.…”