Редактирование: PDHB

Pyruvate dehydrogenase E1 component subunit beta, mitochondrial precursor (EC 1.2.4.1) (PDHE1-B) [PHE1B]

==Publications==

{{medline-entry
|title=Oxidative Damage to the TCA Cycle Enzyme [[MDH1]] Dysregulates Bioenergetic Enzymatic Activity in the Aged Murine Brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32175745
|abstract=Aging can have profound effects on the mammalian brain leading to neurodegeneration and cognitive impairment. The brain has exceptionally high-energy requirements and is particularly susceptible to damage within its bioenergetic pathways. Here, we asked how the bioenergetic proteome of the murine brain changed with age and how this might affect brain function. Using label-free LC-MS/MS proteomics for the discovery phase and quantitative multiple reaction monitoring LC-MRM-MS/MS for the validation phase, we found dysregulated expression of multiple components of the tricarboxylic acid cycle, which is key for mitochondrial energy production, including SULA2, [[IDH1]], [[IDH2]], [[SDHB]], [[PDHB]], [[MDH1]], FH1, and [[NDUFS3]], in old murine brains. We also saw that the oxidoreductases, thioredoxin and glutaredoxin, were significantly down-regulated in the old mouse brain and showed through MS that this correlated with the accumulation of trioxidation in the key metabolic enzyme [[MDH1]] at Cys137. 3D modeling of [[MDH1]] predicted that the damaged sites were located at the protein active zone, and enzymatic kinetic analysis confirmed that [[MDH1]] function was significantly reduced in the old mouse brain. These findings identify the tricarboxylic acid cycle as a key target of degenerative protein modifications with deleterious effects on the aging brain's bioenergetic function.

|keywords=* DPM
* MRM
* TCA cycle
* aging
* brain
|full-text-url=https://sci-hub.do/10.1021/acs.jproteome.9b00861
}}
{{medline-entry
|title=Neuron-specific knockdown of Drosophila [[PDHB]] induces reduction of lifespan, deficient locomotive ability, abnormal morphology of motor neuron terminals and photoreceptor axon targeting.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29501567
|abstract=Pyruvate dehydrogenase complex deficiency ([[PDC]]D) is a common primary cause of defects in mitochondrial function and also can lead to peripheral neuropathy. Pyruvate dehydrogenase E1 component subunit beta ([[PDHB]]) is a subunit of pyruvate dehydrogenase E1, which is a well-known component of [[PDC]]. In Drosophila melanogaster, the CG11876 (d[[PDHB]]) gene is a homolog of human [[PDHB]]. In this study, we established a Drosophila model with neuron-specific knockdown of d[[PDHB]] to investigate its role in neuropathy pathogenesis. Knockdown of d[[PDHB]] in pan-neurons induced locomotor defects in both larval and adult stages, which were consistent with abnormal morphology of the motor neuron terminals at neuromuscular junctions and mitochondrial fragmentation in brains. Moreover, neuron-specific knockdown of d[[PDHB]] also shortened the lifespan of adult flies. In addition, flies with knockdown of d[[PDHB]] manifested a rough eye phenotype and aberrant photoreceptor axon targeting. These results with the Drosophila model suggest the involvement of [[PDHB]] in peripheral neuropathy.
|mesh-terms=* Animals
* Animals, Genetically Modified
* Axons
* Drosophila melanogaster
* Larva
* Locomotion
* Longevity
* Male
* Mitochondria
* Motor Neurons
* Phenotype
* Photoreceptor Cells, Invertebrate
* Pyruvate Dehydrogenase (Lipoamide)
|keywords=* Compound eye
* Drosophila
* Neuromuscular junction
* Neuron
* PDHB
|full-text-url=https://sci-hub.do/10.1016/j.yexcr.2018.02.035
}}