Abstract
Mitochondria are pivotal organelles in eukaryotic cells. The complex proteome of mitochondria comprises proteins that are encoded by nuclear and mitochondrial genomes. The biogenesis of mitochondrial proteins requires their transport in an unfolded state with a high risk of misfolding. The mislocalization of mitochondrial proteins is deleterious to the cell. The electron transport chain in mitochondria is a source of reactive oxygen species that damage proteins. Mitochondrial dysfunction is linked to many pathological conditions and, together with the loss of cellular protein homeostasis (proteostasis), are hallmarks of ageing and ageing-related degeneration diseases. The pathogenesis of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, has been associated with mitochondrial and proteostasis failure. Thus, mitochondrial proteins require sophisticated surveillance mechanisms. Although mitochondria form a proteasome-exclusive compartment, multiple lines of evidence indicate a crucial role for the cytosolic ubiquitin–proteasome system (UPS) in the quality control of mitochondrial proteins. The proteasome affects mitochondrial proteins at stages of their biogenesis and maturity. The effects of the UPS go beyond the removal of damaged proteins and include the adjustment of mitochondrial proteome composition, the regulation of organelle dynamics and the protection of cellular homeostasis against mitochondrial failure. In turn, mitochondrial activity and mitochondrial dysfunction adjust the activity of the UPS, with implications at the cellular level.
Highlights
Mitochondria are multifunctional organelles in eukaryotic cells
The present article provides an overview of the cellular crosstalk between mitochondria and the ubiquitin– proteasome system (UPS), with a primary focus on protein biogenesis and turnover
It is still unknown whether precursor protein ubiquitination blocks or generally affects mitochondrial import
Summary
Mitochondria are multifunctional organelles in eukaryotic cells. mostly recognized as powerhouses because of their respiratory energy conversion, mitochondria perform various other essential functions. Mitochondria provide iron–sulfur cluster assembly, integrate anabolic and catabolic processes (including amino acid and lipid metabolism) and participate in cellular ion homeostasis and signalling pathways [1,2,3,4,5,6]. Mitochondria are organized into a dynamic network that is shaped by frequent fusion and fission processes [5,12,14] To perform their functions, mitochondria need a set of proteins to build the mitochondrial proteome. Precursors of b-barrel OM proteins use the sorting and assembly machinery (SAM) complex coupled with the TOM for their membrane insertion. Precursor proteins that use TIM23 contain N-terminal targeting sequences that are rich in positively charged amino acids. The diversity/plasticity of the mitochondrial proteome and complexity of its biogenesis require integration with two major cytosolic protein degradation machineries: autophagy and the ubiquitin–proteasome system (UPS). We discuss mitochondrial feedback that affects proteasome function, and impacts protein homeostasis ( proteostasis) at the cellular level
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