Sirt5 Sirtuin 5 plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Sirt5 Sirtuin 5 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
SIRT5 is a member of the sirtuin family with unique enzymatic activities including desuccinylation, demalonylation, and deglutarylation, primarily localized to mitochondria.
| Attribute |
Value |
| Gene Symbol |
SIRT5 |
| Full Name |
Sirtuin 5 |
| Chromosomal Location |
6p23 |
| NCBI Gene ID |
83737 |
| OMIM |
604603 |
| Ensembl ID |
ENSG00000124587 |
| UniProt |
Q9NXE1 |
SIRT5 exhibits multiple enzymatic activities in mitochondria:
- Desuccinylation: Removes succinyl groups from lysine residues (primary activity)
- Demalonylation: Removes malonyl groups from proteins
- Deglutarylation: Removes glutaryl groups from proteins
- NAD+-dependent deacetylase: Lower activity compared to other sirtuins
Key substrates include:
- GLUD1: Regulates glutamate dehydrogenase, impacting ammonia detoxification
- HMGCS2: Regulates ketogenesis
- SDH: Succinate dehydrogenase activity modulation
- CPS1: Carbamoyl phosphate synthetase 1, first step of urea cycle
- SIRT5 expression is altered in AD brain
- Regulates mitochondrial metabolism in neurons
- Succinylome analysis reveals SIRT5 targets in AD models
- Maintains mitochondrial complex I function
- Protects against MPTP-induced dopaminergic toxicity
- SIRT5 has dual roles in cancer metabolism
- Often upregulated in certain cancers; context-dependent effects
SIRT5 is expressed in:
SIRT5 is being explored as a therapeutic target:
- SIRT5 inhibitors: May have applications in certain cancers
- SIRT5 activators: Potential for neurodegeneration (preclinical)
- Du Y, et al. SIRT5 regulates the mitochondrial succinylome. Cell Metab. 2011;14(5):714-725. PMID:22100468
- Rardin MJ, et al. SIRT5 regulates the mitochondrial lysine succinylome. Cell Metab. 2013;18(6):920-933. PMID:24332042
- Ushio H, et al. SIRT5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2013;339(6119):361-365. PMID:23212245
Sirt5 Sirtuin 5 plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
The study of Sirt5 Sirtuin 5 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
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- PMID:26245252 - Cell signaling in neurodegeneration