MOTS-c vs VIP (Vasoactive Intestinal Peptide)

MOTS-c

MOTS-c is a 16-residue peptide encoded by a short open reading frame within the mitochondrial gene for 12S ribosomal RNA. It belongs to the mitochondrial-derived peptides, a small group that also includes humanin, which is encoded in the 16S rRNA gene. Since it was first described in the mid-2010s it has been studied mainly in cultured cells and in mice, with attention to glucose and lipid handling in skeletal muscle and to cellular responses to metabolic stress. Human data are limited and consist mostly of measurements of its circulating levels in observational studies.

VIP (Vasoactive Intestinal Peptide)

VIP, or vasoactive intestinal peptide, is a 28-residue amidated neuropeptide found in central and peripheral neurons and in the gut wall. It belongs to the secretin–glucagon family and is most closely related to pituitary adenylate cyclase-activating polypeptide (PACAP), with which it shares receptors. First isolated from intestinal tissue and named for its action on blood vessels, it is now studied as a neurotransmitter, a smooth-muscle signal and a messenger between the nervous and immune systems. Most of the literature comes from cell, tissue and animal studies. Synthetic VIP has been examined in small human studies, including in pulmonary conditions, but it is cleared from the circulation within a few minutes, which complicates that work.

How MOTS-c acts

The first cell and mouse studies reported that MOTS-c inhibits the folate pathway and, with it, de novo purine synthesis, so that the purine intermediate AICAR accumulates. This nucleotide mimics AMP and activates AMP-activated protein kinase (AMPK), a sensor of cellular energy status. Later work reported that under metabolic or oxidative stress the peptide moves from the cytoplasm into the nucleus, where it associates with transcription factors including NRF2 and alters the expression of stress-response genes. Most of this mechanistic evidence comes from cell and rodent models, and human mechanistic data are scarce.

How VIP (Vasoactive Intestinal Peptide) acts

VIP binds two class B G-protein-coupled receptors, VPAC1 and VPAC2, with similar affinity, and binds the PACAP-preferring PAC1 receptor much more weakly. Both VPAC receptors couple mainly to Gs, raising cyclic AMP and activating protein kinase A, although coupling to other G proteins has been described. In immune cell cultures this signalling has been reported to alter cytokine production and T-cell differentiation. In the suprachiasmatic nucleus, mouse studies indicate that VIP acting at VPAC2 helps synchronise the neurons of the circadian clock. In smooth muscle preparations it has been examined as a relaxant signal.

The records side by side

• Type: MOTS-c, Mitochondrial-derived peptide (MDP); VIP (Vasoactive Intestinal Peptide), Neuropeptide (vasoactive intestinal peptide)
• Length: MOTS-c, 16 amino acids; VIP (Vasoactive Intestinal Peptide), 28 amino acids
• Molecular weight: MOTS-c, 2174.6 g/mol; VIP (Vasoactive Intestinal Peptide), 3326.8 g/mol
• Molecular formula: MOTS-c, C101H152N28O22S2; VIP (Vasoactive Intestinal Peptide), C147H237N43O43S

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.