PINK1: Linking Mitochondrial Health and Parkinson's disease

Mon, 08/26/2013 - 11:46

Parkinson's disease is a degenerative disorder of the central nervous system, which involves the loss of dopaminergic neurons in the brain and gives rise to tremors, rigidity and slowness of movement. In the majority of cases there is no known cause; however mutations in a number of specific genes have been implicated. Amongst these are mutations in PTEN-induced putative kinase 1 (PINK1) that give rise to a recessively-inherited early-onset form of the disease, which typically begins before the age of 50 (1).

The PINK1 protein is a serine/threonine kinase that is highly expressed in heart, skeletal muscle and testis, and at lower levels in brain, placenta, liver, kidney, pancreas, prostate, ovary and small intestine. It is localized to mitochondria (2), where it is membrane-anchored. Mitochondria provide >90% of the energy in all eukaryotic cells through oxidative phosphorylation (3), and are enriched in neurons to provide the energy that is required for synaptic transmission. Abnormalities in mitochondrial morphology, maintenance and function have long been observed in PD patients (4).

Western Blot: PINK1 Antibody Western Blot: PINK1 Antibody

PINK1 is known to protect against mitochondrial dysfunction during cellular stress. Healthy, polarized mitochondria express low levels of PINK1, whereas the protein accumulates on damaged mitochondria due to impairment of its transport to the inner mitochondrial membrane (1). This PINK1 accumulation ultimately results in mitophagy - the degradation of mitochondria by autophagocytosis.

Valente, E.M. et. al. have demonstrated the mitochondrial localization of PINK1 by using PINK1 antibodies to immunofluorescently stain COS-7 cells transfected with tagged PINK1 protein (2). They have also used PINK1 antibodies to probe Western blots of lysates prepared from the transfected cells, showing PINK1 staining to be significantly stronger in the mitochondrially-enriched fraction as compared to the cytoplasmic fraction. However, experiments investigating the role of PINK1 to date have been limited by the availability of appropriate cellular models, meaning that researchers have had to rely on such transfected, over-expressing cell lines, or on cells that have been treated with the mitochondrial uncoupling agent carbonyl cyanide m-chlorophenylhydrazone (CCCP). The death of neuronal cells in Parkinson’s disease is known to be associated with the defects in mitochondrial function that arise from mutations in proteins such as PINK1, however further research is required in order to fully understand the relationship between PINK1, mitochondrial health, and Parkinson’s disease (5).

  1. PMID: 23533695
  2. PMID: 15087508
  3. PMID: 22474616
  4. PMID: 22048001
  5. PMID: 23711354

Novus Biologicals offers various PINK1 reagents for your research needs including:

Written by Emma Easthope

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