Inflammation regulation Flashcards
what is the main structure and molecules used in the mitochondria?
what is mtDNA?
mitochondrial DNA; circular double strand
37 genes
limited repair potential and highly prone to damage (oxidation stress) and mutation
how does the mitochondria undergo quality control?
- mitochondrial dynamics (fusion and fission)
- mitochondrial biogenesis
- mitophagy (destroyed)
what is fission/fusion mechanism of mitochondria?
fission: mitochondria division
fusion: mitochondria seperation
different molecules involved-
fission: DRP1
fusion: MFN1, MFN2, OPA1
what is the fission/fusion mechanism in relation to OXPHOS?
fission - less efficient for OXPHOS (mitochondria stress)
fusion - more efficient for OXPHOS
what does mitochondrial oxidation lead to?
cell stress and death
what is mitochondrial biogenesis?
generation of mitochondria
what is mitophagy?
removal of mitochondria by lysosomes
what is the mechanism of mitochondria biogenesis?
- PCG-1a regulates mitochondria biogenesis
- regulates the nuclear expression of TFAM
- signals mtDNA transcription/replication
- allowing mitochondria replication
what is the mechanism of mitophagy?
- primarily initated by dsyfunctioned mitochondria
- stabilisation of pink1 at the OMM and activation of Parkin
- mitochondria primed for degradation through autophagy
- mitochondria degradation in the lysosomes
why is biogenesis and mitophagy essential?
essential for…
1.mitochondria self repair to replace unhealthy mitochondria
2. mitochondrial mass to cope with increase/decrease cellular demands (cellular homesostasis)
how is the regulation of cellular biogenergics and metabolism maintained?
- production of ATP via OXPHOS
- regulation of central metabolic pathways
- mitochondrial mass adjusted to satisfy energy demands
- influenced by mitochondrial dynamics (fusion/fission)
fusion: supports OXPHOS
fission: linked with glycolysis
what is produced during OXPOS?
reactive oxygen species (ROS)
superoxide (o2-)
when is ROS produced?
superoxide (o2-) released in damaged mitochondria
what are mitochondria antioxidants?
used to scavenge ROS to stop cell signalling
Manganese Superoxide dismutase (MnSOD ) Thioredoxin 2 (Trx2)
why are Balanced mitochondrial Redox key for cell signalling?
Posttranslational modifications of proteins
Action on signal transduction
what is senescence?
cellular ageing - end to cell proliferation
what causes senescence?
stress
oncogene activation
telomere shortening (ageing)
what is the function of the mitochondria?
- Regulation of cellular bioenergetics and metabolism
- Control of cell death
- Generation of Reactive oxygen species (ROS)
- Cell differentiation/reprogramming
- Cellular ageing (senescence)
Other key functions:
6. Calcium Transport
7. Steroid synthesis
8. Hormonal signalling
what is the main role of mitochondria in inflammation?
A. Polarization/reprogramming of immune cells
B. Antiviral responses
C. Immune responses to DAMPs
what cells are involved in mitochondria inflammation?
- macrophages
- damage-associated molecular patterns (DAMPs)
what type of cytokines do macrophages produce?
- pro-inflammatory M1
-iNOS
-IL-1b
-TNF-a - tissue repair/angiogenesis M2
-IL10
-TGF-b
-ECM deposition
how are pro-inflammatory cytokines expressed?
Characterized by mitochondrial fission - M1 macrophages
- Glucose utilized for aerobic glycolysis
- Broken Krebs cycle
- High levels of succinate and mtROS
- Stabilization of HIF-1α
= Expression of pro-inflammatory cytokines
how are tissue repair/angiogenesis cytokines expressed?
Characterized by mitochondrial fusion - M2 macrophages
- OXPHOS (more efficient in E production)
- Intact Krebs cycle
