Cleaved PGAM5 dephosphorylates nuclear serine/arginine-rich proteins during mitophagy

Baba, Taiki; Tanimura, Susumu; Yamaguchi, Ayane; Horikawa, Koichiro; Yokozeki, Masashi; Hachiya, Saki; Iemura, Shun‐ichiro; Natsume, Tohru; Matsuda, Noriyuki; Takeda, Kohsuke

doi:10.1016/j.bbamcr.2021.119045

Cited by 2 publications

(2 citation statements)

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“…Mitophagy occurs not only in a pathological state but also in the normal state. PGAM5 would be cleaved and released from mitochondria, then translocate to the cytosol ( Baba et al, 2021 ); PGAM5 was most easily cleaved by the PARL (presenilin-associated rhomboid-like protein) compared with other substrates, especially in cases of cellular stress ( Sekine et al, 2012 ; Lysyk et al, 2021 ). The exact mechanism by which PGAM5 is released to blood is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…This study aimed to examine the relationship between phosphoglycerate mutase 5 (PGAM5) and PD. PGAM5 is a mitochondrial membrane protein with specific Ser/Thr/His protein phosphatase activity and is involved in regulating mitochondrial dynamics, typically in mitophagy ( Yu et al, 2020 ; Baba et al, 2021 ; Cheng et al, 2021 ), while mitophagy plays an active role in maintaining cell function ( Palikaras et al, 2018 ). Cellular stress models have shown that PGAM5 is involved in the link of the PTEN-induced putative protein kinase 1 (PINK1) and Parkin with the ubiquitin pathway as well as a receptor-mediated signaling loop with FUNDC1 ( Chen et al, 2014 ; Lu et al, 2014 ; Wu et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Plasma-derived phosphoglycerate mutase 5 as a biomarker for Parkinson’s disease

Feng

Xiong

et al. 2022

Front. Aging Neurosci.

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BackgroundWe aimed to examine whether plasma-derived phosphoglycerate mutase 5 (PGAM5) can be a biomarker for Parkinson’s disease (PD) diagnosis as well as its association with the severity of motor/non-motor manifestations of PD.MethodsWe enrolled 124 patients with PD (PD group) and 50 healthy controls (HC group). We measured plasma PGAM5 levels using a quantitative sandwich enzyme immunoassay. Patients with PD underwent baseline evaluations using the Unified Parkinson’s Disease Rating Scale (UPDRS), while participants in both groups were evaluated using scales for non-motor manifestations. Receiver operating characteristic curves were used to evaluate the predictive utility of plasma PAMG5 alone and combined with other factors.ResultsPlasma PAMG5 levels were significantly higher in the PD group; the area under the curve (AUC) of plasma PGAM5 levels alone was 0.76. The AUC values for elderly participants and patients without hypertension were 0.78 and that for was 0.79. Notably, plasma PGAM5 levels combined with plasma oligomeric α-synuclein (α-syn) and the score of the REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK) showed AUC values of 0.80 and 0.82. Multivariable logistic analysis revealed that plasma PAMG5 levels were independently associated with PD (odds ratio,1.875 [95% confidence interval 1.206–2.916], p = 0.005) but not the severity of motor/non-motor manifestations of PD.ConclusionPlasma PGAM5 is an independent biomarker for PD, especially among elderly patients (age > 60 years) and patients without hypertension. The predictive utility of PGAM5 was improved when combined with plasma oligomeric α-syn or the RBDQ-HK score.

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Section: Discussionmentioning

confidence: 99%