Neuroscience Institute, Italian National Research Council (CNR), Venetian Institute of Molecular Medicine, 35131, Padova, Italy.
Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, Italy.
Biochem Biophys Res Commun. 2018 May 27;500(1):65-74. doi: 10.1016/j.bbrc.2017.05.041. Epub 2017 May 10.
In recent years, our idea of mitochondria evolved from "mere" energy and metabolite producers to key regulators of many cellular functions. In order to preserve and protect their functional status, these organelles engage a number of dynamic processes that allow them to decrease accumulated burden and maintain their homeostasis. Indeed, mitochondria can unite (fusion), divide (fission), position themselves strategically in the cell (motility/trafficking) and if irreversibly damaged or dysfunctional eliminated (mitophagy). These dynamic processes can be controlled both by mitochondrial and cellular signalling pathways, hence allowing mitochondria to tune their function to the cellular needs. Among the regulatory mechanisms, reversible phosphorylation downstream the cyclic AMP (cAMP) signalling cascade was shown to deeply influence mitochondrial dynamics. This review explores the emerging evidence suggesting that cAMP is a key player in the orchestration of mitochondrial fusion/fission, motility and mitophagy, extending the repertoire of this second messenger, which is now recognised as a major regulator of mitochondrial homeostasis.
近年来,我们对线粒体的认识已经从“仅仅”是能量和代谢物的产生者演变为许多细胞功能的关键调节者。为了保持和保护其功能状态,这些细胞器参与了许多动态过程,使它们能够减少积累的负担并维持其体内平衡。事实上,线粒体可以融合(融合)、分裂(裂变)、在细胞中战略性地定位(运动/运输),如果不可逆转地受损或功能失调则被消除(自噬)。这些动态过程可以通过线粒体和细胞信号通路来控制,因此允许线粒体根据细胞的需求来调节其功能。在调节机制中,下游环腺苷酸 (cAMP) 信号级联的可逆磷酸化被证明深度影响线粒体动力学。这篇综述探讨了新出现的证据,表明 cAMP 是协调线粒体融合/裂变、运动和自噬的关键因素,扩展了这种第二信使的作用范围,现在它被认为是线粒体动态平衡的主要调节剂。