Biology subjects

Kaya, I.

Publications and source records attributed to Kaya, I..

3 recordsLinked to original sources

bioRxiv2025

Met-ID: An Open-Source Software for Comprehensive Annotation of Multiple On-Tissue Chemical Modifications in MALDI-MSI

Here, we introduce Met-ID, a graphical interface software designed to efficiently identify metabolites from MALDI-MSI datasets. Met-ID enables annotation of m/z features from any type of MALDI-MSI experiment, involving either derivatizing or conventional matrices. It utilizes structural information for derivatizing matrices to generate a subset of targets that contain only functional groups specific to the derivatization agent. The software is able to identify multiple derivatization sites on the same molecule, facilitating identification of the derivatized compound. This ability is exemplified by FMP-10, a reactive matrix that assists the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups. Met-ID also permits users to recalibrate data with known m/z ratios, boosting confidence in mass match results. Furthermore, Met-ID includes a database featuring MS2 spectra of numerous chemical standards, consisting of neurotransmitters and metabolites derivatized with FMP-10, alongside peaks for FMP-10 itself, all accessible directly through the software. The MS2 spectral database supports user-uploaded spectra and enables comparison of these spectra with user-provided tissue MS2 spectra for similarity assessment. Although initially installed with basic data, Met-ID is designed to be customizable, encouraging users to tailor the software to their specific needs. While several MSI-oriented software solutions exist, Met-ID stands out as a pioneer in seamlessly combining both MS1 and MS2 functionalities. Developed in alignment with the FAIR Guiding Principles for scientific software, Met-ID is freely available as an open-source tool on GitHub, ensuring wide accessibility and collaboration.

bioinformatics↗

bioRxiv2024

RUVBL1 and RUVBL2 are druggable MYCN regulators in neuroblastoma.

High-risk neuroblastoma is characterized by MYCN amplification and high MYCN or MYC gene expression. These patients have a poor prognosis and there is an urgent need for more effective drugs. While strategies to develop inhibitors that directly target the MYC proteins have remained largely unsuccessful, recent preclinical studies have identified ATR, a key protein of the DNA damage response, as a promising alternative therapeutic target. Here we identified a strong RUVBL1 and RUVBL2 signature in transcriptomics data derived from different MYCN-driven mice tumors treated with ATR inhibitors. The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this protein complex results in a strong reduction of MYC signaling, cell cycle arrest, DNA damage and apoptosis. We confirmed the association with MYCN and identified the RUVBL genes as independent prognosticators in human primary neuroblastoma data.

cancer biology↗

bioRxiv2024

The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain.

The highly conserved CHCHD2 and CHCHD10 are small mitochondrial proteins residing in the intermembrane space. Recently, mutations in the CHCHD2 and CHCHD10 genes have been linked to severe disorders, including Parkinsons disease and amyotrophic lateral sclerosis. In cultured cells, a small fraction of CHCHD2 and CHCHD10 oligomerize to form a high molecular weight complex of unknown function. Here, we generated a whole-body Chchd2 knockout mouse to investigate the in vivo role of CHCHD2 and its protein complex. We show that CHCHD2 is crucial for sustaining full motor capacity, normal striatal dopamine levels, and lipid homeostasis in the brain of adult male mice. We also demonstrate that in mouse tissues, CHCHD2 and CHCHD10 exist exclusively as a high molecular weight complex, whose levels are finely tuned under physiological conditions. In response to mitochondrial dysfunction, the abundance and size of the CHCHD2-CHCHD10 complex increases, a mechanism conserved across different tissues. Although the loss of CHCHD2 does not abolish CHCHD10 oligomerization, it enhances cell vulnerability to mitochondrial stress, suggesting that CHCHD2 is protective against mitochondrial damage. Our findings uncover the role of CHCHD2 in preserving tissue homeostasis and provide important insights into the involvement of the CHCHD2-CHCHD10 complex in human diseases.

neuroscience↗