Biology subjects

Forny, P.

Publications and source records attributed to Forny, P..

3 recordsLinked to original sources

bioRxiv2026

Dynamic protein phosphorylation shapes mitochondrial catalysis, import, and architecture

Phosphorylation is a pervasive mitochondrial protein post-translational modification, yet the extent of its influence over mitochondrial functions remains unclear. To identify dynamic mitochondrial phosphoisoforms, we profiled the phosphoproteome of AML12 cells following individual genetic perturbations of 10 resident mitochondrial phosphatases. Guided by these results, we investigated the functional implications of phosphorylation on mitochondrial processes related to catalysis, import, and morphology. We find that phosphorylation of adenylate kinase 2 suppresses its nucleotide binding and catalytic activity. Elevated phosphorylation proximal to the mitochondrial targeting sequence of branched chain ketoacid dehydrogenase kinase disrupts its import and processing, resulting in enhanced catabolism of branched chain amino acids. Most notably, we discover extensive phosphorylation on proteins involved in mitochondrial cristae architecture, including multiple members of the MICOS complex and ATP synthase, upon silencing the phosphatase PGAM5. Collectively, our work connects reversible phosphorylation and resident phosphatases to the regulation of diverse mitochondrial processes.

molecular biology↗

bioRxiv2023

One-Hour Phosphoproteome Analysis with the Orbitrap Astral Mass Spectrometer

Owing to its roles in cellular signal transduction, protein phosphorylation plays critical roles in myriad cell processes. That said, detecting and quantifying protein phosphorylation has remained a challenge. We describe the use of a novel mass spectrometer (Orbitrap Astral) coupled with data-independent acquisition (DIA) to achieve rapid and deep analysis of human and mouse phosphoproteomes. With this method we map approximately 30,000 unique human phosphorylation sites within a half-hour of data collection. The technology was benchmarked to other state-of-the-art MS platforms using both synthetic peptide standards and with EGF-stimulated HeLa cells. We applied this approach to generate a phosphoproteome multi-tissue atlas of the mouse. Altogether, we detected 81,120 unique phosphorylation sites within 12 hours of measurement. With this unique dataset, we examine the sequence, structural, and kinase specificity context of protein phosphorylation. Finally, we highlight the discovery potential of this resource with multiple examples of novel phosphorylation events relevant to mitochondrial and brain biology.

systems biology↗

bioRxiv2021

Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria

Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria (MMAuria), present unique challenges to energetic homeostasis by disrupting energy producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut) type MMAuria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared to littermate controls, along with a relative reduction in lean mass but increase in fat mass. Brown adipose tissue showed a process of whitening, in line with lower body surface temperature and lesser ability to cope with cold challenge. Mutant mice had dysregulated plasma glucose, delayed glucose clearance and a lesser ability to regulate energy sources when switching from the fed to fasted state, while liver investigations indicated metabolite accumulation and altered expression of peroxisome proliferator-activated receptor and Fgf21-controlled pathways. Together, these indicate hypometabolism, energetic inflexibility and increased stores at the expense of active tissue as energy shortage consequences.

physiology↗