The emerging role of the mitochondrial-derived peptide humanin in stress resistance

Abstract

The discovery of humanin, a novel, mitochondrial-derived peptide, has created a potentially new category of biologically active peptide. As more research unravels the endogenous role of humanin as well as its potential pharmacological use, its role in stress resistance has become clearer. Humanin protects cells from oxidative stress, serum starvation, hypoxia, and other insults in vitro and also improves cardiovascular disease as well as Alzheimer's disease in vivo. In this review, we discuss the emerging role of humanin in stress resistance and its proposed mechanism of action.

Figure 1

The humanin open reading frame (ORF). Humanin is encoded by an ORF within the gene for the 16s ribosomal subunit within the mitochondrial genome.

Figure 2

Function of specific amino acid residues within humanin. Mutational analysis of humanin has allowed for the importance of each amino acid to be elucidated. Important amino acids are marked with their function as noted in the key.

Figure 3

Humanin's mechanism of action and interacting partners. Humanin has shown to have both intracellular and extracellular mechanisms of action. Many of its potential effects are mediated by the FPRL receptor as well as the trimeric WSX1/CNTF/gp130 receptor. Intracellularly, it interacts with many different proteins acting as a pro-survival signal.

Figure 4

Alignment of mitochondrial humanin with possible nuclear homologs. Ten different nuclear-encoded humanin (HN) homologs have been reported with all but one encoding for slightly different proteins than humanin. *Humanin-like protein 8 has a reported polymorphism that would cause it to be identical to mitochondrially encoded humanin.