PT  - JOURNAL ARTICLE
AU  - Janin Lautenschläger
AU  - Sara Wagner-Valladolid
AU  - Amberley D. Stephens
AU  - Ana Fernández-Villegas
AU  - Colin Hockings
AU  - Ajay Mishra
AU  - James D. Manton
AU  - Marcus J. Fantham
AU  - Meng Lu
AU  - Eric J. Rees
AU  - Clemens F. Kaminski
AU  - Gabriele S. Kaminski Schierle
TI  - Intra-mitochondrial proteostasis is directly coupled to alpha-synuclein and Amyloid β 1-42 pathology
AID  - 10.1101/561134
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 561134
4099  - http://biorxiv.org/content/early/2020/01/27/561134.short
4100  - http://biorxiv.org/content/early/2020/01/27/561134.full
AB  - Mitochondria have long been implicated in Parkinson’s disease (PD), however, it is not clear how mitochondrial impairment and alpha-synuclein pathology are coupled. We report here that intra-mitochondrial protein homeostasis plays a major role in alpha-synuclein fibril elongation, as interference with intra-mitochondrial proteases and mitochondrial protein import significantly aggravate alpha-synuclein aggregation. In contrast, direct inhibition of mitochondrial complex I, increase in intracellular calcium concentration or formation of reactive oxygen species (ROS), all of which have been associated with mitochondrial stress, did not affect alpha-synuclein pathology. We further demonstrate that similar mechanisms are involved in Amyloid β 1-42 (Aβ42) aggregation, suggesting that mitochondria are directly capable of influencing cytosolic protein homeostasis of aggregation-prone proteins.