Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells

Abstract

Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knockdown of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs. Knockdown of MTUS1 disturbed the elongated mitochondrial network and induced the formation of perinuclear clusters of mitochondria. Importantly, mitochondrial motility and fusion were suppressed, whereas generation of reactive oxygen species was increased in MTUS1 knockdown ECs. Mechanistically, we showed that the N-terminal coiled-coil domain of MTUS1 interacted with the mitochondrial membrane proteins, mitofusin-1 and mitofusin-2, to maintain mitochondrial morphology in ECs. This study illustrated a novel role of MTUS1 in mitochondrial morphology and EC angiogenic responses.-Wang, Y., Huang, Y., Liu, Y., Li, J., Hao, Y., Yin, P., Liu, Z., Chen, J., Wang, Y., Wang, N., Zhang, P. Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

AT2 receptor interacting protein 1 (ATIP1) mediates COX-2 induction by an AT2 receptor agonist in endothelial cells

“…We observed only the ATIP1 isoform in HUVECs ( Supplemental Fig. 1 (C) ), which is in accord with previous reports [ 29 , 30 ].…”

“…Seibold et al used forced expression analysis of ATIP1 [ 29 ] and Wang et al used polyclonal antibody against ATIP [ 30 ] to demonstrate that ATIP1 localizes mainly to mitochondria. Wang et al reported that ATIP1 appeared in two bands in their expression system, which is consistent with our result ( Supplemental Fig.…”

Dynamic changes of muscle insulin sensitivity after metabolic surgery

“…Likewise, MTUS1 , possibly contributing to protection against pro-inflammatory response of endothelial cells 54 , may be involved in the anti-inflammatory defense at 2 weeks. In addition, MTUS1 has recently been shown to be involved in mitochondrial motility, fusion and in the maintenance of mitochondrial morphology 55 and its reduction at 2 weeks may serve to support the evidence for alterations of mitochondrial content and function early after surgery. At 52 weeks, downregulated genes comprise interferon-γ mediated signaling, in line with the time course of inflammatory markers of the present study and the lower expression of inflammation-related genes in a previous study 56 .…”

Simple to Complex: The Role of Actin and Microtubules in Mitochondrial Dynamics in Amoeba, Yeast, and Mammalian Cells

“…Apart from neurons, studies in other mammalian cells have linked microtubules to fission, specifically through microtubule-associated proteins (MAPs). For example, in mammalian endothelial cells, microtubule-associated tumor suppressor 1 (Mtus1) binds to mitofusins, fusion-regulating proteins on the outer mitochondrial membrane, and helps mediate fusion [ 56 ]. Knocking out Mtus1 results in decreased fusion and shorter mitochondria [ 56 ].…”