Functional characterization of mammalian inositol 1,4,5-trisphosphate receptor isoforms: a role of calcium sensor region

Cell biology of inflammasome activation

A comprehensive overview of the complex world of the endo- and sarcoplasmic reticulum Ca2+-leak channels.

The role of Bcl-2 proteins in modulating neuronal Ca2+ signaling in health and in Alzheimer's disease.

The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs.

https://www.mdpi.com/2073-4409/10/7/1593/pdf

The Influence of Mitochondrial Dynamics and Function on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease

Balancing ER-Mitochondrial Ca2+ Fluxes in Health and Disease

Mutations in WFS1 (which encodes Wolframin, WFS1) and CISD2 (which encodes CDGSH iron sulfur domain 2) result in Wolfram syndrome (WS), a rare genetic disorder that starts with juvenile diabetes an...

Uniting the divergent Wolfram syndrome–linked proteins WFS1 and CISD2 as modulators of Ca2+ signaling

Recent advances in understanding IP3R function with focus on ER-mitochondrial Ca2+ transfers

Calcium ions (Ca2+) operate as important messengers in the cell, indispensable for signaling the underlying numerous cellular processes in all of the cell types in the human body. In neurons, Ca2+ signaling is crucial for regulating synaptic transmission and for the processes of learning and memory formation. Hence, the dysregulation of intracellular Ca2+ homeostasis results in a broad range of disorders, including cancer and neurodegeneration. A major source for intracellular Ca2+ is the endoplasmic reticulum (ER), which has close contacts with other organelles, including mitochondria. In this review, we focus on the emerging role of Ca2+ signaling at the ER–mitochondrial interface in two different neurodegenerative diseases, namely Alzheimer’s disease and Wolfram syndrome. Both of these diseases share some common hallmarks in the early stages, including alterations in the ER and mitochondrial Ca2+ handling, mitochondrial dysfunction and increased Reactive oxygen species (ROS) production. This indicates that similar mechanisms may underly these two disease pathologies and suggests that both research topics might benefit from complementary research.

https://www.mdpi.com/2073-4409/11/12/1963/pdf?version=1655542352

Jens Loncke

Papers

Balancing ER-Mitochondrial Ca2+ Fluxes in Health and Disease

Uniting the divergent Wolfram syndrome–linked proteins WFS1 and CISD2 as modulators of Ca2+ signaling

Recent advances in understanding IP3R function with focus on ER-mitochondrial Ca2+ transfers

Dysregulated Ca2+ Homeostasis as a Central Theme in Neurodegeneration: Lessons from Alzheimer’s Disease and Wolfram Syndrome

The ER-mitochondria interface, where Ca2+ and cell death meet.