Biology subjects

Yalcin, D.

Publications and source records attributed to Yalcin, D..

3 recordsLinked to original sources

bioRxiv2026

ULK1-linked mitophagy promotes cardiac hypoxia tolerance in the blind mole-rat

Blind mole-rats (BMRs) thrive in chronically hypoxic subterranean environments, displaying exceptional cardiac resilience to conditions that rapidly induce failure in other mammals. Here, we integrate in vivo physiology, multi-omics profiling, mitochondrial analyses, and genome editing to uncover an evolved cardioprotective program in BMRs. Under acute 0% O2 exposure, BMRs exhibit markedly prolonged survival compared to mouse. At the molecular level, BMR hearts undergo coordinated metabolic remodeling, restrained inflammatory signaling, and enhanced genome maintenance. Functionally, BMR cardiac mitochondria suppress high-flux oxidative phosphorylation and reverse electron transport-associated ROS following hypoxia, indicating intrinsic adaptation to oxygen collapse. Hypoxia selectively activates AMPK-mTOR-ULK1 dependent mitophagy, and pharmacological manipulation demonstrates that mitophagy is required for BMR cardiomyocyte survival during hypoxia-reoxygenation stress. Finally, we identify a BMR-specific insertion in ULK1 and demonstrate that introduction of this sequence into rat cardiomyocytes enhances hypoxia tolerance in a mitophagy-dependent manner. These findings reveal an evolutionarily tuned mitochondrial quality-control strategy that enables extreme cardiac resilience to hypoxia.

cell biology↗

bioRxiv2025

Stem cells actively suppress regenerative plasticity in human colon

Insights into intestinal stem cell functioning during homeostasis and repair have been predominantly derived from genetic mouse models. This is in stark contrast to the largely unexplored situation in the human gut, where the underlying mechanisms and stimuli that induce regeneration are poorly understood. Here, we developed genetic strategies to characterize fluorescently labelled LGR5+ stem cells in normal human colon organoids. In parallel, we made diphtheria toxin-mediated cell type ablation compatible with human cells, thereby enabling in-depth interrogation of the sequence of events during depletion and reappearance of stem cells. Following LGR5+ stem cell depletion, most of the remaining epithelial cells entered a regenerative state characterized by fetal-like expression programs. Strikingly, this regenerative response was already initiated before stem cell loss, indicative of active communication between functional stem cells and progeny during homeostasis. We identified inactivation of retinoid X receptor (RXR) as a crucial trigger to initiate the regenerative response in colonocytes, with human colon stem cells being the producer of the RXR stimulus retinoic acid. Thus, stem cell-derived retinoic acid actively suppresses the regenerative state in colonocytes, explaining how surviving cells sense stem cell loss.

cell biology↗

bioRxiv2024

In Vitro Generation and Characterization of The Wu Syndrome Model That Causes Mental Retardation in Neural Cell Lines

Wu Syndrome, also known as X-Linked Wu Type Intellectual Developmental Disorder, is caused by a mutation in the GRIA3 (Glutamate Ionotropic Receptor AMPA Type Subunit 3) gene located at position 25 on the X chromosome. GRIA3 encodes iGluR3, a subunit of the AMPA (-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, which plays a critical role in rapid excitatory synaptic transmission in the central nervous system. This receptor is essential for learning, memory, and the processes of long-term depression (LTD) and long-term potentiation (LTP). Despite its significance, Wu Syndrome remains under-researched and lacks effective treatments. Notably, some genetic variants have been identified, but many, including the W637S variant, are still unstudied. This study pioneers the development of a Wu Syndrome model in neural cell lines using genetic modification techniques to identify and characterize new GRIA3 variants. By focusing on variants such as G833R and W637S, this research provides novel insights into their effects on GRIA3 function, paving the way for potential therapeutic strategies. This is the first study to explore the responses of neural cells to these mutations in vitro, thereby contributing valuable knowledge toward understanding and treating Wu Syndrome.

molecular biology↗