Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration

Abstract

Inflammation is increasingly implicated in neurodegenerative disease pathology. As no acquired pathogen appears to drive this inflammation, the question of what does remains. Recent advances indicate damage-associated molecular pattern (DAMP) molecules, which are released by injured and dying cells, can cause specific inflammatory cascades. Inflammation, therefore, can be endogenously induced. Mitochondrial components induce inflammatory responses in several pathological conditions. Due to evidence such as this, a number of mitochondrial components, including mitochondrial DNA, have been labeled as DAMP molecules. In this review, we consider the contributions of mitochondrial-derived DAMPs to inflammation observed in neurodegenerative diseases.

Keywords: damage-associated molecular pattern; mitochondria; neurodegeneration; neuroinflammation; sterile inflammation.

Figure 1

Hypothesized mechanism of mitochondrial-derived damage-associated molecular pattern molecule released in the central nervous system. (A) Neurons can release mitochondria (neuronal mitochondria are shown in red) to astrocytes, where they then undergo mitophagy (orange star shape). In addition, astrocytes can release mitochondria (astrocyte mitochondria are shown in blue) to neurons, under conditions of bioenergetic stress. (B) If the process of mitochondrial exchange between neurons and astrocytes malfunctions (X), then mitochondria and their components could be released into the extracellular space and initiate neuroinflammation.