Hidden phenotypes of PINK1/Parkin knockout mice

被引:13
|
作者
Paul, Swagatika [1 ,2 ]
Pickrell, Alicia M. [2 ]
机构
[1] Virginia Maryland Coll Vet Med, Grad Studies Biomed & Vet Sci, Blacksburg, VA 24601 USA
[2] Virginia Polytech Inst & State Univ, Sch Neurosci, Blacksburg, VA 24061 USA
来源
关键词
PINK1; Parkin; knockout mouse; mitophagy; MITOCHONDRIAL-DNA DELETIONS; PARKIN-DEFICIENT MICE; GMP-AMP SYNTHASE; RECESSIVE JUVENILE PARKINSONISM; ALPHA-SYNUCLEIN; PINK1-DEPENDENT PHOSPHORYLATION; MITOPHAGY MECHANISMS; TRANSCRIPTION FACTOR; MEDIATED MITOPHAGY; MTDNA MAINTENANCE;
D O I
10.1016/j.bbagen.2021.129871
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PINK1, a serine/threonine ubiquitin kinase, and Parkin, an E3 ubiquitin ligase, work in coordination to target damaged mitochondria to the lysosome in a process called mitophagy. This review will cover what we have learned from PINK1 and Parkin knockout (KO) mice. Systemic PINK1 and Parkin KO mouse models haven't faithfully recapitulated early onset forms of Parkinson's disease found in humans with recessive mutations in these genes. However, the utilization of these mouse models has given us insight into how PINK1 and Parkin contribute to mitochondrial quality control and function in different tissues beyond the brain such as in heart and adipose tissue. Although PINK1 and Parkin KO mice have been generated over a decade ago, these models are still being used today to creatively elucidate cell-type specific functions. Recently, these mouse models have uncovered that these proteins contribute to innate immunity and cancer phenotypes.
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页数:9
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