Molecular evolution of proteins mediating mitochondrial fission–fusion dynamics

Sinha, Sansrity

doi:10.1002/1873-3468.13356

Cited by 17 publications

(10 citation statements)

References 86 publications

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“…Similarly to other members of the dynamin superfamily, mitofusins have a modular domain organization confirmed also by a recent evolutionary analysis (Purkanti and Thattai 2015;Sinha and Manoj 2019) ( Fig. 1a).…”

Section: Topology and Domain Composition Of Mitofusinssupporting

confidence: 69%

A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin

et al. 2019

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Mitochondria are dynamic organelles characterized by an ultrastructural organization which is essential in maintaining their quality control and ensure functional efficiency. The complex mitochondrial network is the result of the two ongoing forces of fusion and fission of inner and outer membranes. Understanding the functional details of mitochondrial dynamics is physiologically relevant as perturbations of this delicate equilibrium have critical consequences and involved in several neurological disorders. Molecular actors involved in this process are large GTPases from the dynamin-related protein family. They catalyze nucleotide-dependent membrane remodeling and are widely conserved from bacteria to higher eukaryotes. Although structural characterization of different family members has contributed to understand molecular mechanisms of mitochondrial dynamics in more detail, the complete structure of some members as well as the precise assembly of functional oligomers remain largely unknown. As increasing structural data becomes available, the domain modularity across the dynamin superfamily emerged as a foundation for transfer the knowledge towards less characterized members. In this review we will first provide an overview of the main actors involved in mitochondrial dynamics. We then discuss recent example of computational methodologies for the study of mitofusin oligomers, and present how the usage of integrative modeling in conjunction with biochemical data can be an asset in progress the still challenging field of membrane dynamics.

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Section: Topology and Domain Composition Of Mitofusinssupporting

confidence: 69%

A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin

et al. 2019

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“…There are several proteins involved in the dynamics (fission and fusion) and morphology of the mitochondria (Karbowski and Youle, 2003; Olichon et al, 2006; Brooks and Dong, 2007; Song et al, 2008; Autret and Martin, 2010; Silva et al, 2013; Sinha and Manoj, 2019). One of these is the optic atrophy 1 protein (OPA1) (Olichon et al, 2006; Garcia et al, 2018; Lee and Yoon, 2018).…”

Section: Nf-κb Controls Mitochondrial Dynamicsmentioning

confidence: 99%

What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion?

Albensi

2019

Front. Cell Dev. Biol.

261

175

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A large body of literature supports the idea that nuclear factor kappa B (NF-κB) signaling contributes to not only immunity, but also inflammation, cancer, and nervous system function. However, studies on NF-κB activity in mitochondrial function are much more limited and scattered throughout the literature. For example, in 2001 it was first published that NF-κB subunits were found in the mitochondria, including not only IkBα and NF-κB p65 subunits, but also NF-κB pathway proteins such as IKKα, IKKβ, and IKKγ, but not much follow-up work has been done to date. Upon further thought the lack of studies on NF-κB activity in mitochondrial function is surprising given the importance and the evolutionary history of both NF-κB and the mitochondrion. Both are ancient in their appearance in our biological record where both contribute substantially to cell survival, cell death, and the regulation of function and/or disease. Studies also show NF-κB can influence mitochondrial function from outside the mitochondria. Therefore, it is essential to understand the complexity of these roles both inside and out of this organelle. In this review, an attempt is made to understand how NF-κB activity contributes to overall mitochondrial function – both inside and out. The discussion at times is speculative and perhaps even provocative to some, since NF-κB does not yet have defined mitochondrial targeting sequences for some nuclear-encoded mitochondrial genes and mechanisms of mitochondrial import for NF-κB are not yet entirely understood. Also, the data associated with the mitochondrial localization of proteins must be yet further proved with additional experiments.

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“…Particularly, fusion and fission events are crucial for the mitochondria quality control (MQC) [93]. Fusion events are mediated by core enzymes of mitofusin1(Mfn1) and mitofusin2 (Mfn2) for OMM fusion, and optic atrophy gene 1 (OPA1) for IMM fusion [94]. Fusion redistributes mitochondrial content in the presence of mild and temporary stressors to "dilute" the damage of partially dysfunctional areas.…”

Section: Mitochondrial Damagementioning

confidence: 99%

Regulation of Membrane Phospholipid Homeostasis in Neurodegenerative Diseases

Quan¹,

Bakovic²

2020

obm geriatr

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Neurodegenerative diseases (NDs) are a diverse group of neuropathological diseases that are currently incurable due to the irreversible neuronal loss. At the present rate of the world population growth, it is projected that the number of ND cases will double by the year of 2050. With treatments only available for symptom management and relief, disease prevention may yield significant benefits. Recently, there had been association drawn between the disruption of phospholipid (PL) homeostasis and the progression of NDs. Pathological developments were observed in cellular processes including autophagy, maintenance of mitochondrial integrity, and management of tissue oxidative stress. As PLs actively participate in the regulation of these cellular pathways and in neuronal signal transduction for the maintenance of an optimally functioning nervous system, their homeostasis is tightly controlled via an intricate system of interconversion and metabolism. Therefore, in this review, the contribution of a homeostatic PL pool and the detrimental effects by the lack thereof, are discussed in detail as it relates to ND development.

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Molecular evolution of proteins mediating mitochondrial fission–fusion dynamics

Cited by 17 publications

References 86 publications

A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin

A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin

What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion?

Regulation of Membrane Phospholipid Homeostasis in Neurodegenerative Diseases

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