Biology subjects

Sandbichler, A. M.

Publications and source records attributed to Sandbichler, A. M..

3 recordsLinked to original sources

bioRxiv2026

A novel role for Oxaloacetate Decarboxylase FAHD1 in cardiomyocyte maturation

Mitochondrial metabolism undergoes dramatic reprogramming during postnatal cardiac maturation, yet the enzymatic regulators that ensure continuity of TCA cycle flux in this period remain incompletely defined. FAHD1 is a mitochondrial oxaloacetate decarboxylase (ODx) with proposed roles in modulating the activity of Complex II of the electron transport chain (ETC), but its physiological relevance in vivo has remained unclear. Here, we identify FAHD1 as a critical regulator of mitochondrial function with strong impact on cardiomyocyte (CM) maturation. Using a germline Fahd1-knockout (KO) mouse model, we show that Fahd1 deficiency impairs Complex II respiration, reduces pyruvate levels, and induces a compensatory metabolic shift toward glycolysis and anabolic biosynthesis. Loss of FAHD1 disrupts sarcomere organization, delays the fetal-to-adult myosin isoform switch, and leads to left ventricle systolic dysfunction and cardiomyocyte hypertrophy. These findings highlight FAHD1 as a mitochondrial gatekeeper and potential target for modulating cardiac development and disease.

cell biology↗

bioRxiv2023

13C tracer analysis reveals the landscape of metabolic checkpoints in human CD8+ T cell differentiation

Naive T cells remain in an actively maintained state of quiescence until activation by antigenic signals, upon which they start proliferation and generation of effector cells to initiate a functional immune response. Metabolic reprogramming is essential to meet the biosynthetic demands of the differentiation process, and failure to do so can promote the development of hypofunctional exhausted T cells. Here we used 13C metabolomics and transcriptomics to study the metabolic dynamics of CD8+ T cells in their complete course of differentiation from naive over stem-like memory to effector cells. The quiescence of naive T cells was evident in a profound suppression of glucose oxidation and a decreased expression of ENO1, downstream of which no glycolytic flux was detectable. Moreover, TCA cycle activity was low in naive T cells and associated with a downregulation of SDH subunits. Upon stimulation and exit from quiescence, the initiation of cell growth and proliferation was accompanied by differential expression of T cell regulatory genes and metabolic reprogramming towards aerobic glycolysis with high rates of nutrient uptake, respiration and lactate production. High flux in anabolic pathways imposed a strain on NADH homeostasis, which coincided with engagement of the proline cycle for mitochondrial redox shuttling. With acquisition of effector functions, cells increasingly relied on glycolysis as opposed to oxidative phosphorylation, which paradoxically was not linked to changes in mitochondrial abundance. We further investigated the metabolic phenotype of exhausted T cells, finding that decreased effector function concurred with a reduction in mitochondrial metabolism, glycolysis and amino acid import, and an upregulation of suppressive and quiescence-associated genes, including TXNIP and KLF2. Thus, these results identify multiple features critical for the metabolic reprogramming that supports quiescence, proliferation and effector function of CD8+ T cells during differentiation. Further, an impairment of the same processes in exhaustion suggests that targeting these control points may be useful for both modulation of differentiation and prevention of exhaustion.

immunology↗

bioRxiv2018

Biotrophic interactions disentangled: In-situ localisation of mRNAs to decipher plant and algal pathogen - host interactions at single cell level.

Plant-pathogen interactions follow spatiotemporal developmental dynamics where gene expression in pathogen and host undergo crucial changes. It is of great interest to detect, quantify and localise where and when key genes are active or inactive. Here, we adapt single molecule FISH techniques to demonstrate presence and activity of mRNAs using phytomyxids in their plant and algal host from laboratory and field materials. This allowed to monitor and quantify the expression of genes from the clubroot pathogen Plasmodiophora brassicae, several species of its Brassica hosts, and of several brown algae, including the genome model Ectocarpus siliculosus, infected with the phytomyxid Maullinia ectocarpii. We show that mRNAs are localised along a spatiotemporal gradient, thus providing proof-of-concept of the usefulness of these methods. These methods are easily adaptable to any interaction between microbes and their algal or plant host, and have the potential to increase our understanding of processes underpinning complex plant-microbe interactions.

plant biology↗