PITRM1 Antibodies

Presequence protease, mitochondrial (PITRM1)

Metalloendopeptidase of the mitochondrial matrix which functions in peptide cleavage and degradation rather than in protein processing (PubMed:10360838, PubMed:16849325, PubMed:19196155, PubMed:24931469). Has an ATP-independent activity (PubMed:16849325).

Specifically cleaves peptides in the range of 5 to 65 residues (PubMed:19196155). Shows a preference for cleavage after little polar residues and before basic residues, but with no positional preference (PubMed:10360838, PubMed:19196155, PubMed:24931469).

Gene Information

Human
Gene Name:	PITRM1
Uniprot:	Q5JRX3
Entrez:	10531

Family

Belongs to:
peptidase M16 family

Alternative Names

EC 3.4.24; EC 3.4.24.-; hPreP; Metalloprotease 1; MGC138192; MGC141929; pitrilysin metallopeptidase 1; Pitrilysin metalloproteinase 1mitochondrial; PreP

Molecular Weight

Mass (kDA):
117.413 kDA

Genomic Context

Human
Location:	10p15.2
Sequence:	10; NC_000010.11 (3137727..3172841, complement)

Tissue Specificity

Widely expressed. Expressed at higher level in muscle and heart compared to brain, pancreas, liver, lung and placenta.

Subcellular Localizations

Mitochondrion matrix.

Diseases

• Alzheimer's Disease
• Cardiovascular Diseases
• Obesity
• Lymphomatoid Granulomatosis
• Chronic Kidney Disease
• Kidney Diseases
• Kidney Failure, Chronic

• Hypokinesia

Interacting Proteins

• APP

Pathways

• Proteolysis
• Glomerular Filtration

PTMs

• Cleavage

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/PITRM1

Best Uses Of The PITRM1 Marker

PITRM1-induced Alzheimer’s Disease is being treated using a variety therapeutic approaches. The PITRM1 marker may be a therapeutic target in this disease, and future studies will focus on identifying novel PITRM1 agonists. A new therapeutic approach focuses on increasing activity of IDE, a protein responsible for compensating for the loss PITRM1 from the brain.

PITRM1 acts as a mitochondrial Ab scanner

This anti-mitochondria antibody reacts with Human cell homogen and can be stored at -20degC for up to a year or 4degC for one month. The cost of the blocker peptide is dependent on its length. The BosterBio PITRM1 antibody can be purchased from the manufacturer. The anti-mitochondrial antibody is available in a number of forms and is scalable. Boster scientists can submit their results for any species or application and are eligible to receive product credits. Scientists around the world can enjoy the benefits of this product.

It may be a therapeutic option for Alzheimer's.

Molecular mechanisms of the apoptotic process include alterations in mitochondrial membrane potential. Inhibition of PITRM1 induces a response to mitochondrial stress known as the uncoupled cellular response (UPRmt), which has been implicated in familial AD. The researchers also observed an upregulation of ATF4, DDIT3, HSP60, and mitochondrial proteases in iPSC-derived neurons. The researchers also found that neurons with PITRM1 knockouts had higher levels Ab. A protein that is associated to Alzheimer's disease.

The researchers discovered that a recessive mutation in the PITRM1 gene causes a syndrome that progresses slowly, characterized by a combination of mental retardation, spinocerebellar ataxia, and cognitive decline. The study involved two families from a small Norwegian coastal town with a population of 200. Two of the siblings were undoubtedly affected, while one additional sibling had a peripheral neuropathy. However, the research on the fifth patient was stopped by cancer.

PITRM1 can be mutated in many other genes, as well as the PITRM1 gene. PITRM1 mutations can cause PITRM1's electrostatic interactions to be disrupted, leading to decreased enzyme activity. PITRM1 is also known to cause interference with mitochondrial protein transfer and cell proteostasis. These factors are associated with the development Alzheimer’s disease.

The study suggests PITRM1 may be involved in the treatment of dementia. PITRM1-deficient mice develop a significant amount of amyloid beta peptides and abnormal neuronal death in the brain. The embryonally fatal mice were found. This suggests that PITRM1 mutant mice have neurodegenerative traits similar to adult onset dementia. Furthermore, PITRM1-deficient mice exhibit hindlimb clasping, impaired motor coordination, and basal ganglia-related movement control.

It has been implicated in synaptic pathology

There is a new disorder associated with recessive PITRM1 mutations: an early onset neurodegenerative syndrome characterized by epilepsy, orofacial automatism, delayed motor and language development, and psychosis. This case comes from a Norwegian coastal community. The first described family contained 200 individuals. Two of these were undoubtedly affected. One sibling had peripheral nerve disease, but refused to receive an investigation. The fifth sibling was diagnosed with cancer and died before DNA could even be obtained.

Double staining with MAP2 showed that mice expressing PITRM1 had neuronal mitochondria targeted by the PITRM1 protein. Only 10% of CD11b+ microglia were positive for PITRM1 expression, while only 4% of GFAP+ astrocytes were positive for it. Additionally, PITRM1 expression decreased in old mAPP hippocampal neurons, as well as in those who were subject to high levels Ab.

A deficiency in PITRM1 causes mitochondrial proteostasis to be inhibited and activation for the UPRmt. This decreases the UPS's ability to degrade cytosolic proteins. UPS overload leads to the accumulation of APP, an increase in Ab species, and a higher Ab42/40 ratio. PITRM1 deficiency prevents the production NAD+, which is essential for Ab proteotoxicity.

However, the exact mechanism of PITRM1 has not been fully explained. PITRM1 expression did not decrease the mouse's endogenous Ab level, but it did inhibit excess mitochondrial fission by aged AD mice. However, mPITRM1-knockout mice had a significantly lower level of Mfn2, a mitochondrial protein that is involved in fusion.

Activated PITRM1 could induce mitochondrial proteostasis. TDP43 and APP overproduction is associated with the accumulation of MTS within the mitochondria. The presence of PITRM1 in the brain may be a risk factor for amyloid accumulating diseases. There is not yet any conclusive evidence to link PITRM1 variants and AD. The current study was the largest ever conducted in humans.

It may improve mitochondrial biogenesis

A new study has shown that Boster Bio, a dietary supplement, may increase mitochondrial biogenesis in adipocytes. The product contains FCCP, a trifluromethoxy carbonyl cyanide phenyl hydrazone, and an inhibitor of SIRT1. These results suggest that SIRT1 may have an impact upon adipocytes' mitochondrial function. These promising results are not conclusive. However, more research is needed to confirm the effectiveness of Boster Bio in increasing mitochondrial biogenesis.

The company has developed a commercial kit for mitochondrial isolation. To obtain a sample, fresh liver was obtained from a tank containing four fish and placed in a solution containing 10 mM KH2PO4, 250 mM sucrose, and 5 mM ethylenediamine tetraacetic acid. The liver tissue was then homogenized in 10mL of cold media using a refrigerated centrifuge. The supernatant then was collected in a new centrifuge tub.

Mitochondrion is an organelle that generates ATP. They also play a vital role in many cellular functions. A few inherited diseases can lead to impaired mitochondrial function. Impaired mitochondrial activity can cause many neurodegenerative and stroke-related disorders. The body produces Ab that misfolds and self aggregates in many forms. This is responsible for the formation of diffuse amyloid plaques. These plaques can interfere with proteasome function, inhibit mitochondrial Biogenesis, and stimulate inflammatory responses.

A high quality cellular nutrition can enhance cycling performance by improving mitochondrial health. Higher quality mitochondria means stronger and longer working muscles. Boster Bio may be able to enhance mitochondrial biogenesis through a variety of methods. It is important to remember that mitochondrial Biogenesis is an essential component to any exercise program. Exercise promotes positive feedback that aids in the growth of mitochondria. By increasing the number of mitochondria, the quality of mitochondria improves, allowing the muscles to do more work efficiently.

It can affect amyloid pathology

PITRM1 genes are expressed in different brain cells and play a key role in amyloid disease. This marker is versatile and can be used in many studies. Its potential to predict the fates of neuronal proteinaggregates in amyloidosis is making it increasingly important. It also protects against Ab-induced swelling.

The PITRM1 gene product, a metalloprotease, is part of the pitrilysin-oligopeptidase familia. It is a 117kDa enzyme, which degrades unstructured amino acids of 10 to 55 residues. It is an organellar function analogue to the insulin-degrading enzym. This enzyme contains 1037 amino acids and is expressed in skeletal muscle and various brain regions.

PITRM1-deficient mice showed that the protein is involved in the accumulation of amyloid beta and Ab peptides in brain tissue. The study also suggested that PITRM1 might be involved in the pathology in mitochondrial proteostasis in Ab-rich environments. PITRM1 deficient mice also show impaired motor coordination, basal ganglia movement control, and motor coordination.

PITRM1 deficiency has been linked with strong induction UPRmt in 2D models systems. This transcriptional response involves mitochondrial chaperones as well as proteases. However, chronic activation (or UPRmt) can have a negative impact on cell and organismal functions. In conclusion, PITRM1 deficiency leads to an enhanced cellular proteotoxicity and has detrimental consequences for organoid pathology.