Abstract
Mitochondria have their own ATP-dependent proteases that maintain the functional state of the organelle. All multicellular eukaryotes, including filamentous fungi, possess the same set of mitochondrial proteases, unlike in unicellular yeasts, where ClpXP, one of the two matricial proteases, is absent. Despite the presence of ClpXP in the filamentous fungus Podospora anserina, deletion of the gene encoding the other matricial protease, PaLon1, leads to lethality at high and low temperatures, indicating that PaLON1 plays a main role in protein quality control. Under normal physiological conditions, the PaLon1 deletion is viable but decreases life span. PaLon1 deletion also leads to defects in two steps during development, ascospore germination and sexual reproduction, which suggests that PaLON1 ensures important regulatory functions during fungal development. Mitochondrial Lon proteases are composed of a central ATPase domain flanked by a large non-catalytic N-domain and a C-terminal protease domain. We found that three mutations in the N-domain of PaLON1 affected fungal life cycle, PaLON1 protein expression and mitochondrial proteolytic activity, which reveals the functional importance of the N-domain of the mitochondrial Lon protease. All PaLon1 mutations affected the C-terminal part of the N-domain. Considering that the C-terminal part is predicted to have an α helical arrangement in which the number, length and position of the helices are conserved with the solved structure of its bacterial homologs, we propose that this all-helical structure participates in Lon substrate interaction.
Highlights
Mitochondria are essential organelles in all eukaryotes and have many functions aside from the production of energy
We demonstrated that the absence of the mitochondrial Lon protease is tolerated in P. anserina, but leads to a decrease in life span by a factor of 2.5, while overexpression of the PaLon1 gene was previously reported to increase life span by a factor of 1.7 [18]
Loss of the PaLon1 gene is associated with a weak vital staining of Deletion of the PaLon1 gene (DLon1) mitochondria, which is indicative of a decrease in membrane potential, and was observed in an S. pombe Lon deletion strain [13] and human Lon down-regulated cells [20]
Summary
Mitochondria are essential organelles in all eukaryotes and have many functions aside from the production of energy. Mitochondria possess their own set of ATPdependent proteases, which are homologous to bacterial proteases; these include two metalloproteases of the FtsH bacterial family, which are lodged in the mitochondrial inner membrane and two serine proteases, ClpXP and Lon, which are found in the mitochondrial matrix. The ClpXP protease differs from the other proteases; firstly, its ATPase (ClpX) and protease (ClpP) domains are divided into two polypeptides, and secondly, ClpP is absent in most yeasts. While ClpP, but not Lon, is transcriptionally upregulated when an aggregated protein accumulates within the mitochondrial matrix [2,3], the protein levels of the ClpP and Lon proteases appear to decrease or increase together during pathological conditions [4,5]
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