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山羊功能分化骨骼肌中线粒体分裂和融合蛋白的发育动态。

Developmental dynamics of mitochondrial fission and fusion proteins in functionally divergent skeletal muscles of goat.

机构信息

School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India.

Imgenex India Pvt. Ltd., Bhubaneswar, Odisha, India.

出版信息

Physiol Rep. 2024 Jun;12(11):e16002. doi: 10.14814/phy2.16002.

Abstract

During skeletal muscle development, the intricate mitochondrial network formation relies on continuous fission and fusion. This process in larger mammals differs from rodents, the most used animal models. However, the expression pattern of proteins regulating mitochondrial dynamics in developing skeletal muscle remains unexplored in larger mammals. Therefore, we characterized the cellular expression and tissue-level distribution of these proteins during development taking goat as a model. We have performed histological and immunohistochemical analyses to study metabolic features in various muscles. Neonatal muscles display uniform distribution of mitochondrial activity. In contrast, adult muscles exhibit clear distinctions based on their function, whether dedicated for posture maintenance or facilitating locomotion. Mitochondrial fission proteins like DRP-1, MFF, and fusion proteins like MFN-1 and 2 are abundantly expressed in neonatal muscles. Fission proteins exhibit drastic downregulation with limited peripheral expression, whereas fusion proteins continue to express in a fiber-specific manner during adulthood. Locomotory muscles exhibit different fibers based on mitochondrial activity and peripheralization with high SDH activity. The proximity ligation assay between MFN1 and MFN2 demonstrates that their interaction is restricted to subsarcolemmal mitochondria in adult fibers while distributed evenly in neonatal fibers. These differences between postural and locomotory muscles suggest their physiological and metabolic properties are different.

摘要

在骨骼肌发育过程中,复杂的线粒体网络形成依赖于不断的分裂和融合。这个过程在较大的哺乳动物中与啮齿动物(最常用的动物模型)不同。然而,调节线粒体动力学的蛋白质在较大的哺乳动物发育中的表达模式仍未被探索。因此,我们以山羊为模型,研究了这些蛋白质在发育过程中的细胞表达和组织水平分布。我们进行了组织学和免疫组织化学分析,以研究各种肌肉中的代谢特征。新生肌肉显示线粒体活性的均匀分布。相比之下,成年肌肉根据其功能表现出明显的区别,无论是专门用于维持姿势还是促进运动。分裂蛋白,如 DRP-1、MFF,和融合蛋白,如 MFN-1 和 2,在新生肌肉中大量表达。分裂蛋白的表达急剧下调,且仅限于外周表达,而融合蛋白在成年时继续以纤维特异性的方式表达。运动肌肉根据线粒体活性和边缘化表现出不同的纤维,具有高 SDH 活性。MFN1 和 MFN2 之间的邻近连接测定表明,它们的相互作用仅限于成年纤维的肌小节下,而在新生纤维中均匀分布。姿势和运动肌肉之间的这些差异表明它们的生理和代谢特性不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d0/11148127/102c64b001da/PHY2-12-e16002-g005.jpg

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