A fuzzy mitochondrial fusion apparatus comes into focus

Mozdy, Amy D.; Shaw, Janet M.

doi:10.1038/nrm1125

Cited by 123 publications

(82 citation statements)

References 75 publications

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“…In the following section we will review the fission/fusion machinery focusing on the proteins that have been shown to be involved in mammalian cell death (Table 1). For a more detailed discussion of mitochondrial fission/fusion machinery see review [34][35][36][37][38][39][40].…”

Section: Overview Of Mitochondrial Membrane Dynamics Machinementioning

confidence: 99%

Mitochondrial dynamics in the regulation of neuronal cell death

2007

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Mitochondria undergo continuous fission and fusion events in physiological situations. Fragmentation of mitochondria during cell death has been shown to play a key role in cell death progression, including release of the mitochondrial apoptotic proteins. Ultrastructural changes in mitochondria, such as cristae remodeling, is also involved in cell death initiation. Here, we emphasize the important role of mitochondrial fission/fusion machinery in neuronal cell death. Unlike many other cell types such as immortalized cell lines, neurons are distinct morphologically and functionally. We will discuss how this uniqueness presents special challenges in the cellular response to neurotoxic stresses, and how this affects the mitochondrial dynamics in the regulation of cell death in neurons.

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Section: Overview Of Mitochondrial Membrane Dynamics Machinementioning

confidence: 99%

Mitochondrial dynamics in the regulation of neuronal cell death

2007

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“…Mitochondrial fusion proteins, which are nuclear-encoded, are associated with both the outer and inner mitochondrial membranes. In yeast, three components of the mitochondrial fusion machinery are known: Fzo1 (the outer-membrane GTPase), Mgm1 (the intermembrane-space GTPase) and Ugo1 (the outer-membrane protein that links both GTPases) (Mozdy and Shaw, 2003;Sesaki et al, 2003;Sesaki and Jensen, 2004). In mice and other mammals, homologs of two of these proteins have been identified: mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) are homologs of Fzo1, and Opa1 is homologous to Mgm1 Cipolat et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Interspecies mitochondrial fusion between mouse and human mitochondria is rapid and efficient

2007

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A detailed molecular understanding of mitochondrial fusion and fission in mammalian cells is rapidly emerging. In this report, we demonstrate for the first time cross-species mitochondrial fusion between distantly related species using green and red fluorescent proteins targeted to the mitochondrial matrix. We found that mouse mitochondria were able to efficiently fuse to unmodified mitochondria of human cells and that the contents of the mitochondrial matrix were completely mixed in less than 4 h. We also observed that mitochondria from the mtDNA-less (ρ 0 ) mouse cells can homogeneously fuse to the mitochondria of human cells. We were, however, unable to maintain human mitochondrial DNA in the mouse cells. These results indicate that mitochondrial fusion proteins in mouse and human cells have enough functional homology to mediate efficient cross-species mitochondrial fusion, but mouse nuclear and human mitochondrial genomes have not retained functional compatibility with one another.

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“…They supply the cell with ATP generated by oxidative phosphorylation, they are the site of many anabolic and catabolic pathways, they play an essential role in the assembly of Fe/S clusters, and they are key regulators of programmed cell death (Scheffler, 2000;Lill and Mü hlenhoff, 2005;Youle and Karbowski, 2005). Depending on the cell's physiological conditions, mitochondria frequently change their shape and intracellular position (Bereiter-Hahn, 1990;Yaffe, 1999;Griparic and van der Bliek, 2001;Westermann, 2002;Mozdy and Shaw, 2003;Scott et al, 2003;Chen and Chan, 2004). This dynamic behavior is important for a number of cellular processes.…”

Section: Introductionmentioning

confidence: 99%

Nonredundant Roles of Mitochondria-associated F-Box Proteins Mfb1 and Mdm30 in Maintenance of Mitochondrial Morphology in Yeast

Dürr

Escobar-Henriques

Merz

et al. 2006

MBoC

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Mitochondria constantly fuse and divide to adapt organellar morphology to the cell’s ever-changing physiological conditions. Little is known about the molecular mechanisms regulating mitochondrial dynamics. F-box proteins are subunits of both Skp1-Cullin-F-box (SCF) ubiquitin ligases and non-SCF complexes that regulate a large number of cellular processes. Here, we analyzed the roles of two yeast F-box proteins, Mfb1 and Mdm30, in mitochondrial dynamics. Mfb1 is a novel mitochondria-associated F-box protein. Mitochondria in mutants lacking Mfb1 are fusion competent, but they form aberrant aggregates of interconnected tubules. In contrast, mitochondria in mutants lacking Mdm30 are highly fragmented due to a defect in mitochondrial fusion. Fragmented mitochondria are docked but nonfused in Δmdm30 cells. Mitochondrial fusion is also blocked during sporulation of homozygous diploid mutants lacking Mdm30, leading to a mitochondrial inheritance defect in ascospores. Mfb1 and Mdm30 exert nonredundant functions and likely have different target proteins. Because defects in F-box protein mutants could not be mimicked by depletion of SCF complex and proteasome core subunits, additional yet unknown factors are likely involved in regulating mitochondrial dynamics. We propose that mitochondria-associated F-box proteins Mfb1 and Mdm30 are key components of a complex machinery that regulates mitochondrial dynamics throughout yeast’s entire life cycle.

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A fuzzy mitochondrial fusion apparatus comes into focus

Cited by 123 publications

References 75 publications

Mitochondrial dynamics in the regulation of neuronal cell death

Mitochondrial dynamics in the regulation of neuronal cell death

Interspecies mitochondrial fusion between mouse and human mitochondria is rapid and efficient

Nonredundant Roles of Mitochondria-associated F-Box Proteins Mfb1 and Mdm30 in Maintenance of Mitochondrial Morphology in Yeast

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