title: How do yeast sense mitochondrial dysfunction?
abstract: Apart from energy transformation, mitochondria play important signaling roles. In yeast, mitochondrial signaling relies on several molecular cascades. However, it is not clear how a cell detects a particular mitochondrial malfunction. The problem is that there are many possible manifestations of mitochondrial dysfunction. For example, exposure to the specific antibiotics can either decrease (inhibitors of respiratory chain) or increase (inhibitors of ATP-synthase) mitochondrial transmembrane potential. Moreover, even in the absence of the dysfunctions, a cell needs feedback from mitochondria to coordinate mitochondrial biogenesis and/or removal by mitophagy during the division cycle. To cope with the complexity, only a limited set of compounds is monitored by yeast cells to estimate mitochondrial functionality. The known examples of such compounds are ATP, reactive oxygen species, intermediates of amino acids synthesis, short peptides, Fe-S clusters and heme, and also the precursor proteins which fail to be imported by mitochondria. On one hand, the levels of these molecules depend not only on mitochondria. On the other hand, these substances are recognized by the cytosolic sensors which transmit the signals to the nucleus leading to general, as opposed to mitochondria-specific, transcriptional response. Therefore, we argue that both ways of mitochondria-to-nucleus communication in yeast are mostly (if not completely) unspecific, are mediated by the cytosolic signaling machinery and strongly depend on cellular metabolic state.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskiye Gory 1-40, Moscow 119991, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Knorre
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskiye Gory 1-40, Moscow 119991, Russia.
authors.forename: Svyatoslav S
authors.initials: SS
authors.lastname: Sokolov
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskiye Gory 1-73, Moscow 119991, Russia.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Zyrina
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskiye Gory 1-40, Moscow 119991, Russia. ; Institute of Mitoengineering, Moscow State University, Leninskiye Gory 1, Moscow 119991, Russia.
authors.forename: Fedor F
authors.initials: FF
authors.lastname: Severin
keywords: ROS; mitochondria; retrograde signaling; yeast