title: Rat Humanin is encoded and translated in mitochondria and is localized to the mitochondrial compartment where it regulates ROS production.
abstract: Evidence for the putative mitochondrial origin of the Humanin (HN) peptide has been lacking, although its cytoprotective activity has been demonstrated in a variety of organismal and cellular systems. We sought to establish proof-of-principle for a mitochondria-derived peptide (MDP) in a rat-derived cellular system as the rat HN sequence is predicted to lack nuclear insertions of mitochondrial origin (NUMT). We found that the rat HN (Rattin; rHN) homologue is derived from the mitochondrial genome as evidenced by decreased production in Rho-0 cells, and that peptide translation occurs in the mitochondria as it is unaffected by cycloheximide. Rat HN localizes to the mitochondria in cellular subfractionation and immunohistochemical studies. Addition of a HN analogue to isolated mitochondria from rat INS-1 beta cells reduced hydrogen peroxide production by 55%. In summary, a locally bioactive peptide is derived and translated from an open reading frame (ORF) within rat mitochondrial DNA encoding 16S rRNA.
authors.affiliation: Pediatric Endocrinology, Mattel Children's Hospital UCLA; David Geffen School of Medicine at UCLA, USA.
authors.forename: Vladislava
authors.initials: V
authors.lastname: Paharkova
authors.affiliation: Pediatric Endocrinology, Mattel Children's Hospital UCLA; David Geffen School of Medicine at UCLA, USA.
authors.forename: Griselda
authors.initials: G
authors.lastname: Alvarez
authors.affiliation: Pediatric Endocrinology, Mattel Children's Hospital UCLA; David Geffen School of Medicine at UCLA, USA.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Davis School of Gerontology, University of Southern California, USA.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Pediatric Endocrinology, Mattel Children's Hospital UCLA; David Geffen School of Medicine at UCLA, USA. Electronic address: kukwhalee@mednet.ucla.edu.
authors.forename: Kuk-Wha
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C427211:humanin
keywords: Humanin; Mitochondria-derived peptide; Oxidative stress; Rattin