Biology subjects

Urbach, J.

Publications and source records attributed to Urbach, J..

3 recordsLinked to original sources

bioRxiv2024

A novel mechanism of microbial attachment: the flagellar pump of Giardia lamblia

The ability of microbes to attach to biological and inert substrates is a necessary prerequisite for colonization of new habitats. In contrast to well-characterized mechanisms that rely on specific or non-specific chemical interactions between microbe and substrate, we describe here an effective hydrodynamic mechanism of attachment that relies on fluid flow generated by the microbe. The microbe Giardia lamblia, a flagellated protozoan parasite, naturally attaches to the microvilliated surface of the small intestine but is also capable of attaching indiscriminately to a wide range of natural and artificial substrates. By tracking fluorescent quantum dots, we demonstrate a persistent flow between the parasite and substrate generated by a pair of Giardia flagella. Using both experimental measures and computational modeling, we show that the negative pressure generated by this fluid flow is sufficient to generate the previously measured force of attachment. We further show that this dynamically-generated negative pressure allows Giardia to attach to both solid and porous surfaces, thereby meeting the real-world demands of attachment to the microvilliated surface of intestinal cells. These findings provide experimental support for a hydrodynamic model of attachment that may be shared by other ciliated and flagellated microbes.

biophysics↗

bioRxiv2023

SLP2 coordinates MICOS assembly and cristae morphogenesis via MIC13 and YME1L

The MICOS complex subunit MIC13 is essential for mitochondrial cristae organization. Mutations in MIC13 cause severe mitochondrial hepato-encephalopathy displaying defective cristae morphology and loss of the MIC10-subcomplex. Here we identified stomatin-like protein 2 (SLP2) as an interacting partner of MIC13 and decipher a critical role of SLP2 as an auxiliary MICOS subunit, modulating cristae morphology. SLP2 provides a large interaction hub for MICOS subunits and loss of SLP2 leads to drastic alterations in cristae morphology. Double deletion of SLP2 and MIC13 showed reduced assembly of core MICOS subunit, MIC60 into MICOS and dispersion of MIC60-specific puncta, demonstrating a critical role of SLP2-MIC13 in MICOS assembly and crista junction (CJ) formation. We further identified that the mitochondrial i-AAA protease YME1L in coordination either with MIC13 or SLP2 differentially regulates MICOS assembly pathways thereby interlinking MIC13-specific or scaffolding-specific role of SLP2 with quality control and assembly of the MICOS complex. YME1L- depletion in MIC13 KO could restore MIC10-subcomplex and reform the nascent CJ. Taken together, we propose seeder model for MICOS assembly and CJ formation, where SLP2- MIC13 seed the assembly of MIC60 into MICOS complex and promote the formation of CJ by regulating the quality and stability of MIC10-subcomplex.

biochemistry↗

bioRxiv2019

Cristae undergo continuous cycles of fusion and fission in a MICOS-dependent manner

The mitochondrial inner membrane can reshape under different physiological conditions. How and at which frequency this occurs in vivo and what are the molecular players involved is unknown. Here we show using state-of-the-art live-cell stimulated emission depletion (STED) super-resolution nanoscopy that crista junctions (CJs) are dynamically fusing and dividing in a reversible and balanced manner at a timescale of seconds. CJ dynamics is strongly reduced in the absence of the MICOS subunit MIC13. Staining of the cristae membrane using different protein markers or two inner mitochondrial membrane-specific dyes revealed that cristae also undergo continuous cycles of fusion and fission. These processes are dependent on MIC13 and occur at a timescale of seconds, resembling CJ dynamics. Our data further suggest that MIC60 acts as a docking platform pioneering CJ formation. Overall, by employing a variety of advanced imaging techniques including FRAP (Fluorescence-Recovery-After Photobleaching), SPT (Single-Particle-Tracking), live-cell STED and confocal Airyscan microscopy we demonstrate that cristae undergo continuous cycles of fusion and fission in a manner that is mechanistically linked to CJ formation and dynamics.

cell biology↗