Unraveling the Link Between Mitochondrial Dynamics and Neuroinflammation

Abstract

Neuroinflammatory and neurodegenerative diseases are a major public health problem worldwide, especially with the increase of life-expectancy observed during the last decades. For many of these diseases, we still lack a full understanding of their etiology and pathophysiology. Nonetheless their association with mitochondrial dysfunction highlights this organelle as an important player during CNS homeostasis and disease. Markers of Parkinson (PD) and Alzheimer (AD) diseases are able to induce innate immune pathways induced by alterations in mitochondrial Ca2+ homeostasis leading to neuroinflammation. Additionally, exacerbated type I IFN responses triggered by mitochondrial DNA (mtDNA), failures in mitophagy, ER-mitochondria communication and mtROS production promote neurodegeneration. On the other hand, regulation of mitochondrial dynamics is essential for CNS health maintenance and leading to the induction of IL-10 and reduction of TNF-α secretion, increased cell viability and diminished cell injury in addition to reduced oxidative stress. Thus, although previously solely seen as power suppliers to organelles and molecular processes, it is now well established that mitochondria have many other important roles, including during immune responses. Here, we discuss the importance of these mitochondrial dynamics during neuroinflammation, and how they correlate either with the amelioration or worsening of CNS disease.

Plasma derived cell-free mitochondrial DNA originates mainly from circulating cell-free mitochondria

“…These whole types of circulating nucleic acids are now accurately characterized by high throughput sequencing (6,25,34,38,50,51). Despite previous efforts at designing methods, particularly Q-PCR based, for detecting mtDNA from blood cells (13,14,15,20), the standardization of cir-mtDNA quantification has proved to be a challenge, in particular concerning the issue of calibration. We recently designed an optimized method that enables the direct comparison of cir-nDNA and cir-mtDNA in human plasma (10).…”

“…Mitochondria, often referred to as the powerhouses of the cell, help turn the energy coming from the food intake into energy usable by the cell. Mitochondria are also involved in signaling between cells, cell death, heat production, and signaling calcium (14,15). Given its multiple physiological functions, mitochondria has been considered as a potential biomarker of many normal and pathological conditions (14,16,17).…”

Vitamin K2 Holds Promise for Alzheimer’s Prevention and Treatment

“…Mitochondrial impairment in AD has been documented by decades of research, and the connection between mitochondrial dysfunction, neuroinflammation, and neurodegeneration in AD, Parkinson’s disease, and multiple sclerosis has been described [ 74 , 75 ]. In the previously discussed study that exposed an astrocyte culture to hypoxia, pretreatment with MK-7 not only reduced neuroinflammation, but also increased ATP production and suppressed ROS production in hypoxic astrocytes [ 73 ].…”

How Inflammation Pathways Contribute to Cell Death in Neuro-Muscular Disorders

“…Alterations in mitochondrial morphology and dynamics lead to important implications for cellular function. In particular, dysfunctional mitochondria on resident cells, such as microglia and astrocytes, reduce their role in supporting neuronal survival, synaptic functions and local immunity, thus promoting inflammation and cell death [116].…”