Biology subjects

Basoglu, M.

Publications and source records attributed to Basoglu, M..

6 recordsLinked to original sources

bioRxiv2026

Contact-phagy remodels ER-mitochondria contact sites

Membrane contact sites between the endoplasmic reticulum (ER) and other organelles coordinate cellular organization, metabolism and stress responses, yet how these interfaces are selectively remodeled and removed remains poorly understood. Here we identify a selective autophagy pathway that targets defined ER-mitochondria contact-site (ERMCS) subdomains for turnover, a process we term Contact-phagy. The ER-resident chaperone SIGMAR1 forms a functional complex with the ER-phagy receptor CCPG1, and SIGMAR1-CCPG1 nanoclusters define ERMCS-associated sites of autophagy initiation. Contact-phagy is selectively engaged by metabolic and mitochondrial stress and promotes turnover of defined contact-site components without broadly affecting general ER-phagy, mitophagy or bulk autophagy. At these sites, SIGMAR1-CCPG1 function is coupled to mitochondrial fission: MFF promotes DRP1 recruitment to ERMCS, whereas loss of CCPG1 or SIGMAR1 causes abnormal persistence and clustering of DRP1 and MFF, accompanied by altered mitochondrial remodeling. Loss of CCPG1 further disrupts ER-mitochondria organization and mitochondrial function in pancreatic tissue, while pancreatic cancer cells depend on CCPG1 and SIGMAR1 for organelle integrity and bioenergetic capacity. Together, our findings establish Contact-phagy as a selective pathway for the turnover of defined organelle contact site subdomains and suggest a broader principle by which interorganelle interfaces are maintained.

cell biology↗

bioRxiv2026

Shroom3-dependent pillar cell constriction establishes a mechanical threshold for respiratory lamellar stability

How developing organs acquire complex architectures while maintaining tissue integrity under mechanical stress is a fundamental question in mechanobiology. In the gill, pillar cells support the thin respiratory lamellae, but how they withstand hemodynamic forces is unknown. Here, we show that actomyosin-rich contractile apparatuses (CA) in zebrafish pillar cells act as load-bearing units that generate contractile forces and stabilize the lamellae through adhesion to and enclosure of extracellular collagen columns. CA number correlates with pillar cell constriction, linking subcellular architecture to tissue geometry. We further identify Shroom3 and Vinculin b as key regulators of CA assembly and force transmission: shroom3 deficiency or loss of vclb impairs CA formation and reduces pillar cell constriction, while loss of shroom3 causes lamellar collapse. Together, these findings support a mechanical threshold model in which lamellar integrity depends on a minimum number of CAs per pillar cell and establish the gill lamellae as a model for linking subcellular contractility to tissue-scale mechanical stability.

developmental biology↗

bioRxiv2025

Patterned integrin-laminin adhesion coordinates epithelial collective cell migration

Collective cell migration is essential for development, tissue homeostasis, and disease progression. Although integrin-mediated adhesion is well characterized in single migrating cells in vitro, how integrins coordinate collective epithelial migration in vivo is less clear. Using the zebrafish posterior lateral line primordium (pLLP), we show that integrins 3 and 6 are differentially expressed in the trailing and leading regions of the pLLP, respectively, and that their combined loss induces excessive protrusive activity and slows migration. We further identify laminin 5 (Lama5) as a key basement membrane (BM) component underlying migrating pLLP cells. While loss of laminin 5 alone compromises BM integrity without impairing migration, simultaneous depletion of lama5 and itga6b markedly decreases velocity, and ultimately blocks migration. These findings reveal a robust, redundant adhesion machinery that ensures persistent collective migration in vivo and highlight fundamental principles of epithelial dynamics relevant to development and disease.

developmental biology↗

bioRxiv2025

Lifelong development of zebrafish gills: Asymmetries in early vascular patterning predict adult gill architecture

Gills are essential for fish respiration and have a highly specialized cellular architecture enabling efficient gas exchange. Surprisingly, the developmental processes underlying gill formation in zebrafish remain poorly understood. Here, we present for the first time a comprehensive analysis of the morphogenesis of gill arteries, filaments and lamellae during lifelong development. Our results provide important insights into the temporal and spatial pattern of gill angiogenesis, revealing fundamental differences in the formation of lateral versus medial filaments along the dorso-ventral axis. These early asymmetries correlate with, and likely underlie, the structural asymmetries observed in adult gills, which we quantitatively characterize. This indicates that a region-specific developmental programme establishes a blueprint for gill architecture maintained throughout life. We further show that lamellae develop through a complex interplay between endothelial and cranial neural crest-derived pillar cells. Notably, lamellar size, which strongly influences respiratory efficiency, depends on the position of the filament in the arch. Together, our work identifies key cellular and temporal mechanisms driving gill development and provides a framework to investigate broader principles of branching morphogenesis and angiogenesis in vertebrates.

developmental biology↗

bioRxiv2025

Phosphoribosyl ubiquitination of SNARE proteins regulate autophagy in Legionella infection

Legionella pneumophila is an intracellular pathogen that causes Legionnaires disease. The bacteria releases effector proteins some of which remodel the host autophagic-lysosomal pathways. One effector is RavZ, which delipidates ATG8 proteins, making Legionella-infected cells deficient in autophagy. Here we show that SidE effectors mediate the phosphoribosyl ubiquitination (PR-Ub) of autophagic SNARE proteins STX17 and SNAP29. STX17 modification induces recruitment of STX17+ membranes from the endoplasmic reticulum to Legionella-containing phagosomes to form replicative vacuoles. Using proximity labeling, biochemistry and Legionella infection studies, we have discovered a mechanism by which autophagy is hijacked by bacteria to recruit ER membranes to the bacterial vacuole which has autophagy markers but do not fuse with lysosomes. Mass spectrometric identification of PR-Ub sites and mutational studies show that PR-Ub modification of STX17 alters its interaction with ATG14L, which drives the recruitment of ER membranes to the bacterial vacuole in a PI3K dependent manner. On the other hand, PR-Ub of SNAP29 inhibits the formation of the autophagosomal SNARE complex (STX17-SNAP29-VAMP8) by steric hindrance, thereby preventing the fusion of bacterial vacuoles with lysosomes.

cell biology↗

bioRxiv2022

Disruption of the MICOS complex leads to an aberrant cristae structure and an unexpected, pronounced lifespan extension in Podospora anserina

Mitochondria are dynamic eukaryotic organelles involved in a variety of essential cellular processes including the generation of adenosine triphosphate (ATP) and reactive oxygen species (ROS) as well as in the control of apoptosis and autophagy. Impairments of mitochondrial functions lead to aging and disease. Previous works with the ascomycete Podospora anserina demonstrated that mitochondrial morphotype as well as mitochondrial ultrastructure change during aging. The latter goes along with an age-dependent reorganization of the inner mitochondrial membrane leading to a change from lamellar cristae to vesicular structures. Especially from studies with yeast it is known that beside the F1Fo-ATP-synthase and the phospholipid cardiolipin also the mitochondrial contact site and cristae organizing system (MICOS) complex, existing of the Mic60- and Mic10-subcomplex, is essential for proper cristae formation. In the present study, we aimed to understand the mechanistic basis of age-related changes of the mitochondrial ultrastructure. We observed that MICOS subunits are co-regulated at the posttranscriptional level. This regulation partially depends on the mitochondrial iAAA-protease PaIAP. Most surprisingly, we made the counterintuitive observation that, despite the loss of lamellar cristae and of mitochondrial impairments, the ablation of MICOS subunits (except of PaMIC12) leads to a pronounced lifespan extension. Moreover, simultaneous ablation of subunits of both MICOS subcomplexes synergistically increases lifespan, providing formal genetic evidence that both subcomplexes affect lifespan by different and at least partially independent pathways. At the molecular level we found that ablation of Mic10-subcomplex components leads to a mitohormesis-induced lifespan extension, while lifespan extension of Mic60-subcomplex mutants seems to be controlled by another pathway. Overall, our data demonstrate that both MICOS subcomplexes have different functions and play distinct roles in the aging process of P. anserina.

molecular biology↗