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All round, if on one particular hand mitophagy failure contributes to p62 accumulation and association with α-synuclein and PD pathogenesis, Alternatively, p62 is basic together with parkin and pink1 to maintain neuronal homeostasis and survival.
Inside the cellular setting, beneath situations of ATG5 knockdown leading to stalled autophagy, we imaged superior-contrast layers consisting of p62 oligomers enwrapping lipid droplets by cryogenic electron tomography in cellulo, which we identified as calcium phosphate by compositional spectroscopy analysis. Alongside one another, we visualized the cellular ultrastructure of p62 oligomers with high calcium written content as a potential intermediate phase of autophagy initiation.
Biomarkers can facilitate early diagnosis or offer insights into ailment development. As P62 levels fluctuate in various disorders, measuring these fluctuations can function a diagnostic Device.
The study of p62 in numerous ailment states is usually a vital spot of exploration in molecular biology. The significance of p62 transcends basic mobile features, as it performs a vital purpose in the pathology of various health conditions.
p62 continues to be revealed to exert a basic position in the two autophagy and apoptosis regulation as a result of its power to communicate with essential variables regulating these procedures.
This region of investigation holds significant guarantee for producing new ways to be aware of and deal with An array of human diseases.
July 21, 2025 In just our cells operates an outstanding Management and recycling system called autophagy. This method is to blame for mobile housekeeping, breaking down and reusing old or destroyed parts to take care of health. Central to this system is actually a protein formally named Sequestosome-1 (SQSTM1), but far more typically called p62.
When LC3 connects with p62, it may change the structure in the p62 filaments, leading to them to become shorter or to type clumps.
Furthermore, p62 has proven to influence the mechanistic target of rapamycin (mTOR) signaling pathway. mTOR is pivotal in controlling cell development and metabolism in response to nutrients and growth factors.
As being the carboxy terminal UBA (ubiquitin related) area binds and thus recruits ubiquitinated proteins designated for autophagosomal degradation, p62 features to be a cargo receptor for selective autophagy.
Subsequent binding to ubiquitinated proteins, p62 undergoes oligomerization and interacts Together with the autophagosomal membrane protein LC3, Consequently offering the cargo aggregates to the autophagosome [12]. LC3 exerts numerous roles in autophagy which includes membrane fusion, cargo assortment and autophagosome mobilization. LC3/p62 conversation is indispensable for autophagic degradation of polyubiquitinated cargo.
If we could take into account p62 a “benefactor” when it contributes to guard the cells from tumorigenesis or neurodegeneration, we have to think about it a “maleficent” when it is de-controlled or overexpressed Hence causing the alternative results. Discriminating such behaviour gets to be vital to be familiar with the molecular basis of the above mentioned-described illnesses also to carry out ideal focused therapies.
Nevertheless, latest results also propose the protein may well behave oppositely counteracting tumor enhancement and exerting a pro-apoptotic perform [20]. This paragraph aims to critically revise the most recent literature On this regard and go over the oncoJanus
This protein capabilities for a shuttle, determining and transporting cellular squander on the recycling machinery. The functionality of p62 is linked p62 com to human wellness, and disruptions in its activity are implicated in A selection of ailments, such as neurodegeneration and most cancers.