Biology subjects

Reinert, T.

Publications and source records attributed to Reinert, T..

5 recordsLinked to original sources

bioRxiv2026

Universally conserved isoasparylation sustains ribosome biogenesis and function

All living beings use ribosomes to synthesize proteins from -amino acids. Inherited from our common ancestor, a few universally conserved ribosome biogenesis steps, introducing essential ribosomal RNA modifications, have survived to our days. However, it was unknown whether similar primordial core mechanisms could also target ribosomal proteins. Here we show that the assembly and the function of ribosomes depend on the installation of an unusual {beta}-amino acid, isoaspartate, within the ribosomal protein uS11. In bacteria, mitochondria, and plastids, this modification is catalyzed by the metzincin-like hydrolase YbeY, whereas in archaea and eukaryotes, it is introduced by the atypical kinase Fap7. The formation of this strategically positioned isoaspartate enables correct maturation of the small ribosomal subunit to support protein synthesis and normal cell physiology.

biochemistry↗

bioRxiv2026

Single-cell quantification of the iron-neuromelanin balance in dopaminergic neurons across the lifespan

Dopaminergic neurons in the substantia nigra depend on iron for dopamine synthesis but are vulnerable to iron-induced oxidative stress. Many of these neurons synthesize neuromelanin, an iron-chelating pigment that accumulates across the lifespan and makes them vulnerable in Parkinsons disease. It remains unclear whether their selective vulnerability arises from neuromelanin overload or from the release of toxic labile iron from the oversaturated pigment. We quantified iron and neuromelanin at the single-cell level across the lifespan of chimpanzees, a species closely resembling humans in pigment and iron accumulation. Combining quantitative MRI, X-ray fluorescence imaging, and microscopic colorimetry, we found that the iron-to-neuromelanin ratio remains stable with age across large neuronal populations. Chemical equilibrium modeling of the iron binding in neuromelanin indicated that cytosolic labile iron concentrations remain low throughout adulthood. We have found no evidence for neuromelanin saturation or increased iron-mediated toxicity with age. This finding challenges the hypothesis that neuromelanin saturation drives age-related dopaminergic vulnerability. The presented method provides a quantitative framework for studying iron homeostasis in these neurons.

neuroscience↗

bioRxiv2024

Human short association fibers are thinner and less myelinated than long fibers

The size and complexity of the human brain requires optimally sized and myelinated fibers. White matter fibers facilitate fast communication between distant areas, but also connect adjacent cortical regions via short association fibers. The fundamental questions of i) how thick these fibers are and ii) how strongly they are myelinated, however, remain unanswered. We present a comprehensive analysis of [~]400,000 fibers of human white matter regions with long (corpus callosum) and short fibers (superficial white matter). We demonstrate a substantially smaller fiber diameter and lower myelination in superficial white matter than in the corpus callosum. Surprisingly, we do not find a difference in the ratio between axon diameter and myelin thickness (g-ratio), which is close to the theoretically optimal value of [~]0.6 in both areas. For the first time, to our knowledge, we shed light on a fundamental principle of brain organization that will be essential to understand the human brain.

neuroscience↗

bioRxiv2021

Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease

Axonal degeneration determines the clinical outcome of multiple sclerosis (MS), and is thought to result from exposure of denuded axons to immune-mediated damage. We challenge this view after finding in MS and its mouse models that myelin itself increases the risk of axons to degenerate under inflammatory conditions. We propose a model for demyelinating diseases in which for axons that remain myelinated, and thus shielded from the extracellular milieu, dependence from oligodendroglial support turns fatal in an autoimmune disease environment.

neuroscience↗

bioRxiv2020

Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry

In Parkinsons disease, the depletion of iron-rich dopaminergic neurons in substantia nigras nigrosome 1 precedes first motor symptoms by two decades. Monitoring this neuronal depletion at an early disease stage is needed for diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue iron. However, the mechanisms of MRI contrast in substantia nigra are not well understood, hindering the development of specific biomarkers. We showed that the dominant contribution to the effective transverse MRI relaxation rate [Formula] in nigrosome 1 originates from iron accumulated in the neuromelanin of dopaminergic neurons. We linked [Formula] quantitatively to the product of cell density and local iron concentration in dopaminergic neurons, combining quantitative 3D iron histology, biophysical modeling, and quantitative MRI on post mortem brain tissue. This knowledge opens an avenue for monitoring neuronal iron and density in vivo and may be applied to detect early neurodegeneration in Parkinsons disease.

neuroscience↗