mitochondria

Question 1

origin of mitochondria

Answer 1

believed that mitochondria arose early in evolution of eukaryotic cells by endocytosis of bacteria capable of phosphorylation (endosymbiont hypothesis). Inner membrane from bacteria, outer from eukaryote

Question 2

basic structure of mitochondria

Answer 2

outmembrane is semi-permeable. Inner is much less permeable, contains most of machinery for Oxidative phosphorylation, cristae (infoldings of membrane) greatly increase surface area. Central space is known as matrix

Question 3

fissure/fusion of mitochondria

Answer 3

very dynamic, undergo fusion and fission. Fusion plays role in repairing damaged mito and maintaining integrity dependent on GTPases Mfn and OPA1. Fission is required for mitophagy and is dependent on GTPases Fis1 and Drp

Question 4

machinery of mitochondria import

Answer 4

import via TOM (translocase of outer membrane) and TIM (translocase of inner membrane) complexes. TOM is passive, TIME is ATP dependent

Question 5

electron transport and proton gradient

Answer 5

NADH electrons moved to O2 to form H2O. Transfer occurs across inner mitochondria. During the electron transfer, protons are moved from matrix across inner membrane to create proton gradient.

Question 6

proton gradient and ATP production

Answer 6

ATP made by ATP synthase using the protongradient and electrical potential from NADH oxidation. ATP synthase has 2 main parts. F1 and F0. F0 spans inner membrane and froms proton channel. F1: bound to F0, actual enzyme that makes ATP. 3 protons used per one ATP. transported out of mito via ATP-ADP antiporter

Question 7

cell death regulation by mitochondria

Answer 7

cell damage => Bak/Bac-dependent permeabilization of outer membrane => cytochrome c release => joins with cytoplasmic proeins forming apoptosome => activates caspases. Ischemic injury => MPTP-dependent permeabilization of inner and outer membrane => cytochrome release and elimination of proton gradient => no ATP production => ATP synthase turns to ATPase => ATP depletion => necrosis. mito also regulates cytosolic calcium and generates ROS

Question 8

mitochondria quality control

Answer 8

damaged mito produce ROS. Controlled at 3 levels to prevent this: 1) mito proteases (mAAA, iAAA, and Lon) recognize and degrade misfolded proteins. 2) damaged mito can be fixed by fusing to healthy mito, or eliminated by mitophagy. 3) if damage is extensive, goes to apoptosis

Question 9

senescence

Answer 9

mito damage and increased ROS related to senescence and increased sensitivity to neuronal degeneration.

Question 10

mitochondria-related diseases

Answer 10

mutations in mito fusion machinery causes autosomal dominant optic atrophy (OPA1 gene) and Charcot-Marie-Tooth neuropathy type 2A (Mfn2 gene). Mutation of mAAA protease causes hereditary spastic paraplegia. Arsenic works by inhibiting oxidative phosphorylation and ATP production