Abstract
Mitochondria are dynamic, semi-autonomous organelles that execute numerous life-sustaining tasks in eukaryotic cells. Functioning of mitochondria depends on the adequate action of versatile proteinaceous machineries. Fine-tuning of mitochondrial activity in response to cellular needs involves continuous remodeling of organellar proteome. This process not only includes modulation of various biogenetic pathways, but also the removal of superfluous proteins by adenosine triphosphate (ATP)-driven proteolytic machineries. Accordingly, all mitochondrial sub-compartments are under persistent surveillance of ATP-dependent proteases. Particularly important are highly conserved two inner mitochondrial membrane-bound metalloproteases known as m-AAA and i-AAA (ATPases associated with diverse cellular activities), whose mis-functioning may lead to impaired organellar function and consequently to development of severe diseases. Herein, we discuss the current knowledge of yeast, mammalian, and plant AAA proteases and their implications in mitochondrial function and homeostasis maintenance.
Highlights
Mitochondria are multifunctional organelles that play a central role in a broad range of life-sustaining tasks within eukaryotic cells, including adenosine triphosphate (ATP) production, calcium storage, and cofactor-generating pathways such as iron-sulfur cluster biogenesis [1,2,3,4].Mitochondria are key mediators in cell proliferation, differentiation, and death signaling as well as in innate immunity [2,3,5,6]
Broad arrays of mitochondrial functions are accomplished by multifaceted proteome comprised of about 1500 polypeptides that are spread between aqueous and membranous mitochondrial sub-compartments: Outer membrane (OM), intermembrane space (IMS), inner membrane (IM), and matrix [8,9]
Cells 2018, 7, 163 imported into the organelle, and a limited number of mitochondrial proteins (~1%, including few subunits of OXPHOS complexes) are encoded by mitochondrial genome in the organellar matrix [15,16,17]. This imposes a need for precisely synchronized expression, sorting and folding of both nuclear and mitochondrial encoded subunits to enable their subsequent assembly into functional stoichiometric complex in IM
Summary
Mitochondria are multifunctional organelles that play a central role in a broad range of life-sustaining tasks within eukaryotic cells, including adenosine triphosphate (ATP) production, calcium storage, and cofactor-generating pathways such as iron-sulfur cluster biogenesis [1,2,3,4]. Mitochondrial protein content undergoes persistent adaptations to meet cellular needs and quality control From this perspective, IM is challenging mitochondrial sub-compartment. Cells 2018, 7, 163 imported into the organelle, and a limited number of mitochondrial proteins (~1%, including few subunits of OXPHOS complexes) are encoded by mitochondrial genome (mtDNA) in the organellar matrix [15,16,17]. This imposes a need for precisely synchronized expression, sorting and folding of both nuclear and mitochondrial encoded subunits to enable their subsequent assembly into functional stoichiometric complex in IM. This review summarizes the current state of knowledge on pleiotropic functions of AAA proteases and their implications for mitochondrial functions and homeostasis
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