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ATP酶抑制因子1是线粒体ATP合酶结构与功能的组织特异性生理调节因子：深入探究神经元功能

The ATPase Inhibitory Factor 1 is a Tissue-Specific Physiological Regulator of the Structure and Function of Mitochondrial ATP Synthase: A Closer Look Into Neuronal Function.

作者信息

Domínguez-Zorita Sonia, Romero-Carramiñana Inés, Cuezva José M, Esparza-Moltó Pau B

机构信息

Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, (CSIC-UAM), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) ISCIII, Instituto de Investigación Hospital 12 de Octubre, Universidad Autónoma de Madrid, Madrid, Spain.

Salk Institute for Biological Studies, La Jolla, CA, United States.

出版信息

Front Physiol. 2022 Mar 18;13:868820. doi: 10.3389/fphys.2022.868820. eCollection 2022.

DOI:10.3389/fphys.2022.868820
PMID:35620611
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9128019/
Abstract

The ATP synthase is an essential multifunctional enzyme complex of mitochondria that produces most of cellular ATP, shapes the structure of the inner membrane into cristae and regulates the signals that control cell fate or demise. The ATPase Inhibitory Factor 1 (IF1) functions as a physiological regulator of the ATP synthase and thereby controls mitochondrial structure and function, and the retrograde signaling pathways that reprogram nuclear gene expression. However, IF1 is not ubiquitously expressed in mammals, showing tissue-restricted expression in humans and mice and large expression differences between the two species in some tissues. Herein, we summarized key regulatory functions of IF1 for tissue homeostasis, with special emphasis on the deleterious effects that its genetic ablation in neurons has in learning. The development and characterization of tissue-specific mouse models with regulated expression of IF1 will be crucial to disentangle the contribution of the ATP synthase/IF1 axis in pathophysiology.

摘要

ATP合酶是线粒体中一种重要的多功能酶复合体，它产生细胞内大部分的ATP，将内膜结构塑造成嵴，并调节控制细胞命运或死亡的信号。ATP酶抑制因子1（IF1）作为ATP合酶的生理调节因子，从而控制线粒体的结构和功能，以及重编程核基因表达的逆行信号通路。然而，IF1在哺乳动物中并非普遍表达，在人类和小鼠中表现出组织限制性表达，并且在某些组织中两种物种之间存在较大的表达差异。在此，我们总结了IF1对组织稳态的关键调节功能，特别强调其在神经元中的基因缺失对学习产生的有害影响。开发和表征IF1表达受调控的组织特异性小鼠模型对于厘清ATP合酶/IF1轴在病理生理学中的作用至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2386/9128019/177ac7ebd05d/fphys-13-868820-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2386/9128019/5e9b41f4dbf5/fphys-13-868820-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2386/9128019/177ac7ebd05d/fphys-13-868820-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2386/9128019/5e9b41f4dbf5/fphys-13-868820-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2386/9128019/177ac7ebd05d/fphys-13-868820-g002.jpg

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Nat Commun. 2021 Aug 10;12(1):4835. doi: 10.1038/s41467-021-25161-x.
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Downregulation by CNNM2 of ATP5MD expression in the 10q24.32 schizophrenia-associated locus involved in impaired ATP production and neurodevelopment.
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