Suggested origin of mitochondria:
Mitochondria showed up by way of endocytosis of oxidative-phosphorylating bacteria by our distant ancestor(s)
- outer membrane: eukaryotic origin
- Inner membrane: engulfed bacteria
- Generation of ATP
- Regulation of Intracellular Ca2+
How are mitochondrial proteins, imported into the mitochondrial matrix?
Imported via TOM and TIM complexes.
Between TIM and TOM,
- Which one is passive?
- Which one is ATP-dependent?
ATP dep: TIM
Fusion of mitochondria plays key role in?
Fusing with healthy mitochondria to repair damaged mitochondria
-thus “fixing” it
Fission of mitochondria plays key role in?
Mitophagy: targeting mitochondria for degredation via autophagy
Fusion and Fission are dependent on cellular _____.
List the proteins involved
Fusion - Mfn + OPA1
Fission - Fis1 + Drp
Describe how electrons are released from NADH during respiration in mitochondria and what this generates
- NADH is oxidized, freeing up H+
- Protons from mt matrix are pumped across inner membrane
- this generates proton [ ] gradient + electric potential
Describe basic principles of ATP production in mitochondria
ATP is synthesized from:
ADP and Pi coupled with electron transfer (proton gradient/electric potential)
-This is achieved by ATP synthase in IMM (inner Mt mem)
What does ATP synthase consist of?
F0: in IMM and forms proton channel
F1: bound to F0 and is actual enzyme that makes ATP
How does F0 function?
F0 uses the E of proton movement through the channel to generate ATP
How is ATP transported out of the mitochondria?
Describe basic mechanism of apoptotic cell death regulation by mitochondria
- cell damage occurs
- induces Bak/Bax- dependent permeabilization of OMM
- releases cytochrome c
- cytochrome c binds to apoptosomes
- activates caspases (initiating apoptosis)
Describe basic mechanism of necrotic cell death regulation by mitochondria
- Ischemic injury
- Induces MPTP-dependent permeabilization of IMM and OMM
- Cytochromes are released
- eliminates protein gradient
In absence of proton gradient, ATP synthase is converted into what?
- leads to ATP depletion and necrosis
Damaged mitochondria generate excessive amts of?
What does it do?
Reactive oxygen (ROS) - causes cell damage and senescence by oxidating proteins, lipids, and DNA
3 Principles of Mitochondrial quality control during damage
- mitochondrial proteases (mAAA, iAAA, Lon) recognizes and degrades misfolded proteins
- “fixing” by fusing with healthy mt
- inducing apoptotic cell death
role of mt in sensecense
ROS generation by damaged mt induces sensescense by oxidating proteins, lipids, and DNA
Mitochondria-related diseases and gene or protein that is affected
- Optic atropy
- Charcot-Marie-Tooth neuropathy type 2A
- hereditary spastic paraplegia
- mAAA proteases
How does arsenic affect mitochondria?
Inhibits oxidative phosphorylation and inhibiting ATP production