Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Curr Opin Cell Biol ; 88: 102364, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692079

RESUMO

First identified in dividing cells as revolving clusters of actin filaments, these are now understood as mitochondrially-associated actin waves that are active throughout the cell cycle. These waves are formed from the polymerization of actin onto a subset of mitochondria. Within minutes, this F-actin depolymerizes while newly formed actin filaments assemble onto neighboring mitochondria. In interphase, actin waves locally fragment the mitochondrial network, enhancing mitochondrial content mixing to maintain organelle homeostasis. In dividing cells actin waves spatially mix mitochondria in the mother cell to ensure equitable partitioning of these organelles between daughter cells. Progress has been made in understanding the consequences of actin cycling as well as the underlying molecular mechanisms, but many questions remain, and here we review these elements. Also, we draw parallels between mitochondrially-associated actin cycling and cortical actin waves. These dynamic systems highlight the remarkable plasticity of the actin cytoskeleton.


Assuntos
Citoesqueleto de Actina , Actinas , Homeostase , Mitocôndrias , Mitocôndrias/metabolismo , Actinas/metabolismo , Humanos , Animais , Citoesqueleto de Actina/metabolismo , Organelas/metabolismo
2.
Nat Commun ; 15(1): 3793, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714822

RESUMO

Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.


Assuntos
Actinas , Homeostase , Interfase , Mitocôndrias , Dinâmica Mitocondrial , Actinas/metabolismo , Mitocôndrias/metabolismo , Humanos , Forminas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células HeLa , Microtúbulos/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Animais
3.
J Cell Sci ; 136(5)2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36744380

RESUMO

Mitochondrial homeostasis requires a dynamic balance of fission and fusion. The actin cytoskeleton promotes fission, and we found that the mitochondrially localized myosin, myosin 19 (Myo19), is integral to this process. Myo19 knockdown induced mitochondrial elongation, whereas Myo19 overexpression induced fragmentation. This mitochondrial fragmentation was blocked by a Myo19 mutation predicted to inhibit ATPase activity and strong actin binding but not by mutations predicted to affect the working stroke of the motor that preserve ATPase activity. Super-resolution imaging indicated a dispersed localization of Myo19 on mitochondria, which we found to be dependent on metaxins. These observations suggest that Myo19 acts as a dynamic actin-binding tether that facilitates mitochondrial fragmentation. Myo19-driven fragmentation was blocked by depletion of either the CAAX splice variant of the endoplasmic reticulum (ER)-anchored formin INF2 or the mitochondrially localized F-actin nucleator Spire1C (a splice variant of Spire1), which together polymerize actin at sites of mitochondria-ER contact for fission. These observations imply that Myo19 promotes fission by stabilizing mitochondria-ER contacts; we used a split-luciferase system to demonstrate a reduction in these contacts following Myo19 depletion. Our data support a model in which Myo19 tethers mitochondria to ER-associated actin to promote mitochondrial fission.


Assuntos
Actinas , Dinâmica Mitocondrial , Actinas/metabolismo , Miosinas/metabolismo , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo
4.
J Biol Chem ; 299(2): 102906, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36642185

RESUMO

Myosin-19 (Myo19) controls the size, morphology, and distribution of mitochondria, but the underlying role of Myo19 motor activity is unknown. Complicating mechanistic in vitro studies, the identity of the light chains (LCs) of Myo19 remains unsettled. Here, we show by coimmunoprecipitation, reconstitution, and proteomics that the three IQ motifs of human Myo19 expressed in Expi293 human cells bind regulatory light chain (RLC12B) and calmodulin (CaM). We demonstrate that overexpression of Myo19 in HeLa cells enhances the recruitment of both Myo19 and RLC12B to mitochondria, suggesting cellular association of RLC12B with the motor. Further experiments revealed that RLC12B binds IQ2 and is flanked by two CaM molecules. In vitro, we observed that the maximal speed (∼350 nm/s) occurs when Myo19 is supplemented with CaM, but not RLC12B, suggesting maximal motility requires binding of CaM to IQ-1 and IQ-3. The addition of calcium slowed actin gliding (∼200 nm/s) without an apparent effect on CaM affinity. Furthermore, we show that small ensembles of Myo19 motors attached to quantum dots can undergo processive runs over several microns, and that calcium reduces the attachment frequency and run length of Myo19. Together, our data are consistent with a model where a few single-headed Myo19 molecules attached to a mitochondrion can sustain prolonged motile associations with actin in a CaM- and calcium-dependent manner. Based on these properties, we propose that Myo19 can function in mitochondria transport along actin filaments, tension generation on multiple randomly oriented filaments, and/or pushing against branched actin networks assembled near the membrane surface.


Assuntos
Calmodulina , Miosinas , Humanos , Actinas/metabolismo , Cálcio/metabolismo , Calmodulina/metabolismo , Células HeLa , Miosinas/metabolismo
5.
Nature ; 591(7851): 659-664, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658713

RESUMO

Symmetric cell division requires the even partitioning of genetic information and cytoplasmic contents between daughter cells. Whereas the mechanisms coordinating the segregation of the genome are well known, the processes that ensure organelle segregation between daughter cells remain less well understood1. Here we identify multiple actin assemblies with distinct but complementary roles in mitochondrial organization and inheritance in mitosis. First, we find a dense meshwork of subcortical actin cables assembled throughout the mitotic cytoplasm. This network scaffolds the endoplasmic reticulum and organizes three-dimensional mitochondrial positioning to ensure the equal segregation of mitochondrial mass at cytokinesis. Second, we identify a dynamic wave of actin filaments reversibly assembling on the surface of mitochondria during mitosis. Mitochondria sampled by this wave are enveloped within actin clouds that can spontaneously break symmetry to form elongated comet tails. Mitochondrial comet tails promote randomly directed bursts of movement that shuffle mitochondrial position within the mother cell to randomize inheritance of healthy and damaged mitochondria between daughter cells. Thus, parallel mechanisms mediated by the actin cytoskeleton ensure both equal and random inheritance of mitochondria in symmetrically dividing cells.


Assuntos
Actinas/química , Actinas/metabolismo , Mitocôndrias/metabolismo , Mitose , Citoesqueleto de Actina/química , Citoesqueleto de Actina/metabolismo , Animais , Divisão Celular , Linhagem Celular , Citocinese , Retículo Endoplasmático/metabolismo , Hipocampo/citologia , Hipocampo/embriologia , Humanos , Mitocôndrias/química , Neurônios , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...