Elsevier

Mitochondrion

Volume 53, July 2020, Pages 166-177
Mitochondrion

Mitochondrial unfolded protein-related responses across kingdoms: similar problems, different regulators

https://doi.org/10.1016/j.mito.2020.05.009Get rights and content
Under a Creative Commons license
open access

Highlights

  • Each kingdom has apparently developed its specific UPRmt regulators.

  • However, UPRmt activation induces nuclear gene expression of many similar genes.

  • Strategies to resolve mitochondrial dysfunctions are thus partially conserved.

  • We identified conserved genes across kingdoms as candidates for future research.

Abstract

Mitochondria are key components of eukaryotic cells, so their proper functioning is monitored via different mitochondrial signalling responses. One of these mitochondria-to-nuclear ‘retrograde’ responses to maintain mitochondrial homeostasis is the mitochondrial unfolded protein response (UPRmt), which can be activated by a variety of defects including blocking mitochondrial translation, respiration, protein import or transmembrane potential. Although UPRmt was first reported in cultured mammalian cells, this signalling pathway has also been extensively studied in the nematode Caenorhabditis elegans. In yeast, there are no published studies focusing on UPRmt in a strict sense, but other unfolded protein responses (UPR) that appear related to UPRmt have been described, such as the UPR activated by protein mistargeting (UPRam) and mitochondrial compromised protein import response (mitoCPR). In plants, very little is known about UPRmt and only recently some of the regulators have been identified. In this paper, we summarise and compare the current knowledge of the UPRmt and related responses across eukaryotic kingdoms: animals, fungi and plants. Our comparison suggests that each kingdom has evolved its own specific set of regulators, however, the functional categories represented among UPRmt–related target genes appear to be largely overlapping. This indicates that the strategies for preserving proper mitochondrial functions are partially conserved, targeting mitochondrial chaperones, proteases, import components, dynamics and stress response, but likely also non-mitochondrial functions including growth regulators/hormone balance and amino acid metabolism. We also identify homologs of known UPRmt regulators and responsive genes across kingdoms, which may be interesting targets for future research.

Abbreviations

AA
antimycin A
ABC
ATP-binding cassette
ALAAT2
alanine aminotransferase 2
ANAC017
Arabidopsis NAC domain containing protein 17
AOX1a
alternative oxidative 1a
ASP2
aspartate aminotransferase 2
ATF-4
activating transcription factor 4
ATF-5
activating transcription factor 5
ATFS-1
Activating Transcription Factor associated with Stress-1
ATPase
adenosine triphosphatase
bHLH
basic helix-loop-helix
bZIP
basic leucine zipper
C. elegans
Caenorhabditis elegans
CAP
chloramphenicol
CHOP
C/EBP homologous protein
Dox
doxycycline
DVE-1
Defective proVEntriculus 1
EIF2A
eukaryotic initiation factor 2 alpha
EndoG
endonuclease G
ER
endoplasmic reticulum
GPCR
G protein-coupled receptor
IMM
inner mitochondrial membrane
IMS
intermembrane space
IPGAM2
2,3-biphosphoglycerate-independent phosphoglycerate mutase
ISR
integrated stress response
MAGIC
mitochondria as guardian in cytosol
MAPK
mitogen-activated protein kinase
MB
MitoBlock-6
MGE1
mitochondrial grpe 1
mitoCPR
mitochondrial compromised protein import response
mPOS
mitochondrial precursor over-accumulation stress
MRPs
mitochondrial ribosomal proteins
MRR
mitochondrial retrograde regulation
mtDNA
mitochondrial DNA
mtPQC
mitochondrial protein quality control
MTS
mitochondrial targeting sequence
NLS
nuclear localization sequence
NRF1
nuclear respiratory factor 1
OMM
outer mitochondrial membrane
OPA3
optic atrophy 3
OXPHOS
oxidative phosphorylation
ROS
reactive oxygen species
S. cerevisiae
Saccharomyces cerevisiae
SOD2
superoxide dismutase 2
SOT12
sulphotransferase 12
TCA
tricarboxylic acid
TF
transcription factor
TIM
translocase of the inner membrane
TOM
translocase of the outer membrane
TOR
target of rapamycin
UBL-5
Ubiquitin-like protein 5
UPR
unfolded protein response
UPRam
unfolded protein responses activated by protein mistargeting
UPRER
endoplasmic reticulum unfolded protein responses
UPRIMS
UPR in the mitochondrial IMS
UPRmt
mitochondrial unfolded protein response
WT
wild type

Keywords

Mitochondria
Unfolded protein response
Retrograde signalling
UPRmt
UPRam
mitoCPR

Cited by (0)