Neuroprotective effects of ATPase inhibitory factor 1 preventing mitochondrial dysfunction in Parkinson's disease

Chung, InHyeok; Park, Hana; Kang, Jun Mo; Kim, Heyyoung; Hah, Su Min; Kim, Hyeon Soo; Choi, Wonseok; Chung, Ji Hyung; Shin, Min Jeong

doi:10.1038/s41598-022-07851-8

Cited by 8 publications

(3 citation statements)

References 51 publications

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“…For instance, mice with high levels of IF1 exhibit better synaptic transmission and learning, while those with low levels have impaired memory 23 . In addition, it was shown that IF1 administration in a transgenic mouse model of Parkinson's disease prevents mitochondrial impairment and improves motor functions 31 . These observations, mostly derived from animal models, were not confirmed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Plasma Level of ATPase Inhibitory Factor 1 and Intrinsic Capacity in Community-Dwelling Older Adults: Prospective Data From the MAPT Study

Silva

Martinez

Rolland

et al. 2023

The Journals of Gerontology: Series A

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Background Intrinsic capacity (IC) is a concept related to functionality that reflects healthy aging. ATPase inhibitory factor 1 (IF1) is a multifaceted protein that regulates mitochondrial oxidative phosphorylation (OXPHOS), and may be involved in IC. The objective of this study is to investigate the association between plasma levels of IF1 and IC changes in community-dwelling older adults. Methods Community-dwelling older adults from the Multidomain Alzheimer Preventive Trial (MAPT Study) were enrolled in this study. A composite IC score was calculated based on four IC domains: locomotion, psychological dimension, cognition, and vitality (with data available annually over four years of follow-up). Secondary analyses were conducted on the sensory domain (with data available only for one year of follow-up). Mixed-model linear regression adjusted for confounders was conducted. Results A total of 1090 participants with usable IF1 values were included in the study (75.3 ± 4.4 years; 64% females). Compared to the lowest quartile, both the low- and high-intermediate IF1 quartiles were found to be cross-sectionally associated with greater composite IC scores across four domains (βlow-intermediate, 1.33; 95% CI 0.06–2.60 and βhigh-intermediate, 1.78; 95% CI 0.49–3.06). In the secondary analyses, the highest quartile was found to be associated with a slower decline in composite IC scores across five domains over one year (βhigh 1.60; 95% CI 0.06–3.15). The low- and high-intermediate IF1 quartiles were also found to be cross-sectionally associated with greater locomotion (βlow-intermediate, 2.72; 95% CI 0.36–5.08) and vitality scores (βhigh-intermediate, 1.59; 95% CI 0.06–3.12), respectively. Conclusions This study is the first to demonstrate that levels of circulating IF1, a mitochondrial-related biomarker, are associated with IC composite scores in both cross-sectional and prospective analyses among community-dwelling older adults. However, further research is needed to confirm these findings and elucidate the potential underlying mechanisms that may explain these associations.

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Section: Discussionmentioning

confidence: 99%

Plasma Level of ATPase Inhibitory Factor 1 and Intrinsic Capacity in Community-Dwelling Older Adults: Prospective Data From the MAPT Study

Silva

Martinez

Rolland

et al. 2023

The Journals of Gerontology: Series A

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“…Following centrifugation, the protein concentration of the collected supernatant was normalized. 19 After that, the sample cells were incubated at room temperature for 3 h and then probed with assay solution for 30 min at room temperature. With the application of a VICTOR X3 Multilabel Plate Reader (PerkinElmer, Waltham, MA, USA), the absorbance was measured at 450 nm.…”

Section: Methodsmentioning

confidence: 99%

Silencing KLF6 Alleviates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction in Bronchial Epithelial Cells by SIRT4 Upregulation

Wan,

Wang,

Cui

et al. 2024

COPD

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Background The incidence of chronic obstructive pulmonary disease (COPD) is increasing year by year. Kruppel-like factor 6 (KLF6) plays an important role in inflammatory diseases. However, the regulatory role of KLF6 in COPD has not been reported so far. Methods The viability of human bronchial epithelial cells BEAS-2B induced by cigarette smoke extract (CSE) was detected by CCK-8 assay. The protein expression of KLF6 and sirtuin 4 (SIRT4) was appraised with Western blot. RT-qPCR and Western blot were applied to examine the transfection efficacy of sh-KLF6 and Oe-KLF6. Cell apoptosis was detected using flow cytometry. The levels of inflammatory factors IL-6, TNF-α and IL-1β were assessed with ELISA assay. DCFH-DA staining was employed for the detection of ROS activity and the levels of oxidative stress markers SOD, CAT and MDA were estimated with corresponding assay kits. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and Complex I activity were evaluated with JC-1 staining, ATP colorimetric/fluorometric assay kit and Complex I enzyme activity microplate assay kit. With the application of mitochondrial permeability transition pore detection kit, mPTP opening was measured. Luciferase report assay was employed to evaluate the activity of SIRT4 promoter and chromatin immunoprecipitation (ChIP) to verify the binding ability of KLF6 and SIRT4 promoter. Results KLF6 expression was significantly elevated in CSE-induced cells. KLF6 was confirmed to suppress SIRT4 transcription. Interference with KLF6 expression significantly inhibited cell viability damage, cell apoptosis, inflammatory response, oxidative stress and mitochondrial dysfunction in CSE-induced BEAS-2B cells, which were all reversed by SIRT4 overexpression. Conclusion Silencing KLF6 alleviated CSE-induced mitochondrial dysfunction in bronchial epithelial cells by SIRT4 upregulation.

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“…Small-molecule inhibitors of PARP1 activity have shown promising results in cell models . It may also be plausible to supplement cells with NAD + , which appears to inhibit translocation of AIF and activation of the parthanatos cell death pathway. , Other approaches may limit PAR-mediated PS of α-synuclein, which is one of the most upstream components of the pathway.…”

Section: Accumulation Of Poly(adp-ribose) In Neurodegenerative Pathol...mentioning

confidence: 99%

Regulation of Biomolecular Condensates by Poly(ADP-ribose)

et al. 2023

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Biomolecular condensates are reversible compartments that form through a process called phase separation. Post-translational modifications like ADP-ribosylation can nucleate the formation of these condensates by accelerating the self-association of proteins. Poly(ADP-ribose) (PAR) chains are remarkably transient modifications with turnover rates on the order of minutes, yet they can be required for the formation of granules in response to oxidative stress, DNA damage, and other stimuli. Moreover, accumulation of PAR is linked with adverse phase transitions in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In this review, we provide a primer on how PAR is synthesized and regulated, the diverse structures and chemistries of ADP-ribosylation modifications, and protein−PAR interactions. We review substantial progress in recent efforts to determine the molecular mechanism of PAR-mediated phase separation, and we further delineate how inhibitors of PAR polymerases may be effective treatments for neurodegenerative pathologies. Finally, we highlight the need for rigorous biochemical interrogation of ADP-ribosylation in vivo and in vitro to clarify the exact pathway from PARylation to condensate formation.

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Neuroprotective effects of ATPase inhibitory factor 1 preventing mitochondrial dysfunction in Parkinson's disease

Cited by 8 publications

References 51 publications

Plasma Level of ATPase Inhibitory Factor 1 and Intrinsic Capacity in Community-Dwelling Older Adults: Prospective Data From the MAPT Study

Plasma Level of ATPase Inhibitory Factor 1 and Intrinsic Capacity in Community-Dwelling Older Adults: Prospective Data From the MAPT Study

Silencing KLF6 Alleviates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction in Bronchial Epithelial Cells by SIRT4 Upregulation

Regulation of Biomolecular Condensates by Poly(ADP-ribose)

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