SHLP3(Small humanin-like peptide 3)

SHLP3 is a mitochondria-derived peptide belonging to the humanin peptide family, which includes humanin, MOTS-c, and other small humanin-like peptides encoded within the mitochondrial genome. These peptides function as retrograde signaling molecules that influence cellular metabolism and stress adaptation. SHLP3 exhibits cytoprotective properties, including reduction of apoptosis, attenuation of reactive oxygen species generation, and enhancement of mitochondrial metabolic function. Emerging evidence links SHLP3 to regulation of aging-related pathways and metabolic homeostasis. This peptide is used in research on mitochondrial signaling, oxidative stress responses, apoptosis modulation, and age-associated disease mechanisms, supporting studies in longevity and metabolic biology.

Product Name: SHLP3(Small humanin-like peptide 3)

Sequence One Letter Code: H - MLGYNFSSFPCGTISIAPGFNFYRLYFIWVNGLAKVVW - OH

Sequence Three Letter Code: NH2-Met-Leu-Gly-Tyr-Asn-Phe-Ser-Ser-Phe-Pro-Cys-Gly-Thr-Ile-Ser-Ile-Ala-Pro-Gly-Phe-Asn-Phe-Tyr-Arg-Leu-Tyr-Phe-Ile-Trp-Val-Asn-Gly-Leu-Ala-Lys-Val-Val-Trp-COOH

Molecular Weight: 4380.4

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Cancer Disease Research

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Current Research: SHLP3 (Small Humanin-Like Peptide 3) is a mitochondria-derived peptide (MDP) encoded within short open reading frames of the mitochondrial 16S rRNA region. It belongs to the humanin peptide family, which includes humanin, MOTS-c, and additional SHLP isoforms. These peptides represent an expanding class of bioactive signaling molecules that mediate mitochondrial–nuclear communication, often referred to as retrograde signaling. Through this mechanism, mitochondria convey functional status to the nucleus and cytosol, coordinating adaptive responses to metabolic and oxidative stress. Current research increasingly recognizes SHLP3 as a cytoprotective regulator with roles distinct from other family members. Experimental studies demonstrate that SHLP3 reduces apoptosis in multiple cell types exposed to stressors such as serum deprivation, oxidative insult, or mitochondrial dysfunction. Mechanistically, SHLP3 appears to modulate intrinsic apoptotic pathways, influencing mitochondrial membrane potential stability and downstream caspase activation. These effects contribute to preservation of cell viability under stress conditions. A key area of investigation involves SHLP3’s impact on reactive oxygen species (ROS) homeostasis. Mitochondria are both major producers and targets of ROS, and dysregulated redox signaling is implicated in aging and numerous chronic diseases. SHLP3 has been shown to attenuate ROS accumulation, potentially by enhancing mitochondrial efficiency or activating antioxidant response pathways. Studies examine changes in superoxide production, mitochondrial respiration, and expression of antioxidant enzymes following SHLP3 treatment. These findings suggest a role in maintaining mitochondrial integrity during oxidative stress. Metabolic regulation represents another active research domain. SHLP3 has been reported to improve mitochondrial bioenergetic function, including enhanced oxygen consumption rate (OCR) and improved coupling efficiency in certain models. By influencing mitochondrial metabolism, SHLP3 may support adaptive responses during nutrient stress or energetic imbalance. This aligns with broader evidence that mitochondria-derived peptides coordinate systemic metabolic homeostasis, integrating signals related to glucose utilization, lipid oxidation, and cellular energy status. Emerging data link SHLP3 to aging-associated pathways. Mitochondrial dysfunction is a hallmark of aging, and circulating levels of certain MDPs have been observed to change with age. SHLP3’s cytoprotective and metabolic-stabilizing properties have prompted investigation into its potential contribution to longevity and resilience against age-related decline. Experimental models explore its influence on cellular senescence markers, stress resistance, and survival signaling pathways such as AKT and ERK. In age-associated diseases, SHLP3 is being studied in contexts including neurodegeneration, cardiovascular dysfunction, and metabolic syndrome. Its anti-apoptotic and antioxidant effects are particularly relevant in tissues susceptible to mitochondrial impairment, such as neurons and cardiomyocytes. Investigations often employ in vitro stress models combined with mitochondrial functional assays, apoptosis markers (e.g., caspase activity, Annexin V staining), and transcriptomic analysis of stress-response genes. From a signaling perspective, researchers are examining whether SHLP3 interacts with specific cell surface receptors or intracellular targets to mediate its protective effects. While definitive receptor identification remains under investigation, evidence suggests activation of pro-survival signaling cascades and modulation of inflammatory pathways. Comparative analyses with humanin and MOTS-c help delineate functional distinctions among mitochondrial peptides. Methodologically, synthetic SHLP3 is used in dose-response studies assessing cell viability, mitochondrial membrane potential (ΔΨm), ROS production, and metabolic flux. In vivo studies explore systemic metabolic effects, insulin sensitivity, and stress resistance phenotypes. Overall, SHLP3 is a mitochondria-derived peptide with demonstrated cytoprotective and metabolic-regulatory properties. By modulating apoptosis, oxidative stress, and mitochondrial function, it serves as a valuable research tool for investigating mitochondrial signaling networks, aging-related pathways, and metabolic homeostasis. Its role within the expanding field of mitochondrial-derived peptide biology continues to provide insight into how mitochondrial genomic signals influence cellular and systemic resilience.