Humanin-induced autophagy plays important roles in skeletal muscle function and lifespan extension
Biochimica et Biophysica Acta (BBA)-General Subjects, 2022•Elsevier
Background Autophagy, a highly conserved homeostatic mechanism, is essential for cell
survival. The decline of autophagy function has been implicated in various diseases as well
as aging. Although mitochondria play a key role in the autophagy process, whether
mitochondrial-derived peptides are involved in this process has not been explored. Methods
We developed a high through put screening method to identify potential autophagy inducers
among mitochondrial-derived peptides. We used three different cell lines, mice, c. elegans …
survival. The decline of autophagy function has been implicated in various diseases as well
as aging. Although mitochondria play a key role in the autophagy process, whether
mitochondrial-derived peptides are involved in this process has not been explored. Methods
We developed a high through put screening method to identify potential autophagy inducers
among mitochondrial-derived peptides. We used three different cell lines, mice, c. elegans …
Background
Autophagy, a highly conserved homeostatic mechanism, is essential for cell survival. The decline of autophagy function has been implicated in various diseases as well as aging. Although mitochondria play a key role in the autophagy process, whether mitochondrial-derived peptides are involved in this process has not been explored.
Methods
We developed a high through put screening method to identify potential autophagy inducers among mitochondrial-derived peptides. We used three different cell lines, mice, c.elegans, and a human cohort to validate the observation.
Results
Humanin, a mitochondrial-derived peptide, increases autophagy and maintains autophagy flux in several cell types. Humanin administration increases the expression of autophagy-related genes and lowers accumulation of harmful misfolded proteins in mice skeletal muscle, suggesting that humanin-induced autophagy potentially contributes to the improved skeletal function. Moreover, autophagy is a critical role in humanin-induced lifespan extension in C. elegans.
Conclusions
Humanin is an autophagy inducer.
General significance
This paper presents a significant, novel discovery regarding the role of the mitochondrial derived peptide humanin in autophagy regulation and as a possible therapeutic target for autophagy in various age-related diseases.
Elsevier
