SHLP4 (Small humanin-like peptide 4)

SHLP4 is a mitochondria-derived peptide encoded within the mitochondrial genome and a member of the humanin peptide family. These mitochondrial peptides are released into the cytosol and function as signaling molecules that regulate cellular homeostasis. SHLP4 has been reported to promote cell proliferation and may contribute to reduced apoptotic signaling in certain cell types. Emerging studies suggest roles in mitochondrial communication, stress adaptation, and age-associated cellular processes. SHLP4 is used in research investigating mitochondrial–nuclear signaling, metabolic regulation, and mechanisms linking mitochondrial function to cell survival and aging-related disease.

Product Name: SHLP4 (Small humanin-like peptide 4)

Sequence One Letter Code: H - MLEVMFLVNRRGKICRVPFTFFNLSL - OH

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

Molecular Weight: 3132

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Cancer Disease Research

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Current Research: SHLP4 (Small Humanin-Like Peptide 4) is a mitochondria-derived peptide (MDP) encoded within short open reading frames of the mitochondrial 16S rRNA region and belongs to the humanin peptide family. This family includes humanin, MOTS-c, and several SHLP isoforms, all of which are increasingly recognized as bioactive signaling molecules mediating mitochondrial–nuclear communication. Unlike classical mitochondrial proteins involved directly in oxidative phosphorylation, MDPs function as retrograde signals that coordinate cellular adaptation to metabolic and oxidative stress. Mitochondria-derived peptides are translated from the mitochondrial genome and can be released into the cytosol and, in some cases, detected in circulation. They participate in regulatory networks that integrate mitochondrial functional status with nuclear gene expression and cytoplasmic signaling pathways. SHLP4 has emerged as one of the less extensively characterized members of this family, but accumulating data indicate that it plays a role in modulating cell survival and proliferative responses. Current research suggests that SHLP4 promotes cell proliferation in specific cellular contexts. Experimental models have demonstrated increased proliferation rates following SHLP4 treatment, potentially through activation of pro-survival signaling pathways such as ERK/MAPK or PI3K/AKT cascades. These pathways are central to growth factor–mediated cell cycle progression and metabolic adaptation. The proliferative effects of SHLP4 distinguish it functionally from other family members that are primarily associated with cytoprotection or metabolic regulation. In addition to promoting proliferation, SHLP4 may attenuate apoptotic signaling under certain stress conditions. Studies evaluating apoptosis markers—such as caspase activation, Annexin V staining, and mitochondrial membrane potential—suggest that SHLP4 can influence intrinsic apoptotic pathways. By stabilizing mitochondrial function or modulating downstream survival signaling, SHLP4 may contribute to enhanced cellular resilience during metabolic or oxidative stress. The role of SHLP4 in mitochondrial communication is a growing area of investigation. As a mitochondria-encoded peptide, SHLP4 exemplifies the concept that mitochondrial genomes encode signaling factors beyond components of the respiratory chain. These peptides provide a direct molecular link between mitochondrial status and cellular adaptation, influencing nuclear transcriptional programs and stress response pathways. Understanding SHLP4’s targets and receptor interactions remains an active focus of study. Emerging evidence also implicates SHLP4 in age-associated cellular processes. Mitochondrial dysfunction is a hallmark of aging, and alterations in MDP expression have been observed in age-related conditions. SHLP4’s influence on proliferation and apoptosis positions it as a potential modulator of tissue homeostasis during aging. Research is exploring whether changes in SHLP4 levels correlate with cellular senescence, metabolic decline, or susceptibility to degenerative disease. In metabolic research, SHLP4 is examined for its potential effects on mitochondrial respiration, ATP production, and reactive oxygen species (ROS) balance. By influencing mitochondrial bioenergetics and redox signaling, SHLP4 may contribute to broader metabolic homeostasis. Comparative studies with other humanin-like peptides help clarify functional diversity within the family and delineate isoform-specific signaling mechanisms. Methodologically, synthetic SHLP4 is used in cell-based assays measuring proliferation, survival, mitochondrial membrane potential, and signaling pathway activation. Transcriptomic and proteomic analyses are employed to identify downstream targets and pathway alterations following SHLP4 exposure. In vivo studies are beginning to assess systemic metabolic and aging-related effects. Overall, SHLP4 is a mitochondria-derived signaling peptide that contributes to cellular homeostasis through regulation of proliferation, survival pathways, and stress adaptation. As part of the expanding field of mitochondrial-derived peptides, it provides a valuable tool for investigating mitochondrial–nuclear communication, metabolic regulation, and mechanisms linking mitochondrial function to aging and disease-associated cellular dysfunction.