Inside-out submitochondrial particles affect the mitochondrial permeability transition pore opening under conditions of mitochondrial dysfunction

IF 3.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Cristina Algieri , Antonia Cugliari , Patrycja Anna Glogowski , Silvia Granata , Micaela Fabbri , Fabiana Trombetti , Maria Laura Bacci , Salvatore Nesci
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引用次数: 0

Abstract

The inside-out submitochondrial particles (IO-SMPs) showed a strong protective effect against mitochondrial permeability transition pore (mPTP) opening in mitochondria isolated from swine hearts 3 h after explantation. The latter condition was used to emulate situation of mitochondrial damage. We identified that the protective effect of IO-SMPs cannot be attributed to a functional modulation of the enzymatic complexes involved in mPTP formation. Indeed, oxidative phosphorylation and F1FO-ATPase activity were not affected. Conversely, mPTP desensitization might be caused by structural modification. IO-SMP incorporation into the mitochondria can modulate the membrane-bound enzyme complexes' functionality, inducing F1FO-ATPase to be unable to carry out the conformational changes useful for mPTP opening. Thus, the data are a valid starting point for IO-SMP application in the treatment of impaired cardiovascular conditions supported by mPTP opening.
线粒体功能障碍条件下,由内而外的亚线粒体颗粒影响线粒体通透性过渡孔的打开
在猪心脏离体3 h后,由内向外的亚线粒体颗粒(IO-SMPs)对线粒体通透性过渡孔(mPTP)的打开具有较强的保护作用。后一种情况用于模拟线粒体损伤情况。我们发现IO-SMPs的保护作用不能归因于参与mPTP形成的酶复合物的功能调节。事实上,氧化磷酸化和f1fo - atp酶活性并未受到影响。相反,mPTP脱敏可能是由结构修饰引起的。IO-SMP掺入线粒体可以调节膜结合酶复合物的功能,诱导f1fo - atp酶无法进行有利于mPTP打开的构象改变。因此,这些数据为IO-SMP应用于mPTP开放支持的心血管疾病的治疗提供了一个有效的起点。
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来源期刊
Biochimica et Biophysica Acta-Bioenergetics
Biochimica et Biophysica Acta-Bioenergetics 生物-生化与分子生物学
CiteScore
9.50
自引率
7.00%
发文量
363
审稿时长
92 days
期刊介绍: BBA Bioenergetics covers the area of biological membranes involved in energy transfer and conversion. In particular, it focuses on the structures obtained by X-ray crystallography and other approaches, and molecular mechanisms of the components of photosynthesis, mitochondrial and bacterial respiration, oxidative phosphorylation, motility and transport. It spans applications of structural biology, molecular modeling, spectroscopy and biophysics in these systems, through bioenergetic aspects of mitochondrial biology including biomedicine aspects of energy metabolism in mitochondrial disorders, neurodegenerative diseases like Parkinson''s and Alzheimer''s, aging, diabetes and even cancer.
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