Mitochondria Flashcards
Three major functions of mitochondria
1 Generation of ATP 2 Apoptosis 3 Regulation of intracellular Ca ions
Where does all oxidative phosphorylation occur in mitochondria?
On the inner membrane, which is folded into cristae. The cristae folds exist to maximize the surface area which allows for more oxidative phosphorylation to produce more ATP.
What is the permeability of the outer membrane of mitochondria and what are its consequences?
The outer membrane is very porous, containing many pore structures up to a few microns in size, which allows the inter membrane space to rapidly equilibrate with the cytosol, esp for small molecules such as NAD, FAD, ATP, and H+.
What is the permeability of the inner membrane of the mitochondria and what are its consequences?
The inner membrane is very impermeable. It contains many gated channels that allow molecules to cross over under controlled circumstances. This allows for the creation of the H+ gradient used in the production of ATP. This gradient is effectively between the matrix of the mitochondria and the cytosol due to the leaky nature of the outer membrane. Disruption of this process kills cells due to lack of ATP.
What percentage of mitochondrial genes are encoded by the nuclear genome versus the mitochondrial genome?
About 90% are encoded by the nuclear genome, leaving only 10% to be encoded by the mitochondrial genome. However, many of those encoded by the mitochondria are used in oxidative phosphorylation and the health of the mitochondria. Proteins encoded in the nucleus must be imported into the mitochondria.
What advantage did mitochondria impart to early archaea bacteria that likely engulfed them?
The archaea bacteria where anaerobes at the time that photosynthesis developed, increasing levels of O2 in the atmosphere. It is likely that the oxidative phosphorylation activities of mitochondria protected the early archaea bacteria from the effects of this extra oxygen inside the cell.
How do proteins enter the outer membrane of the mitochondria?
The GIP (general import ports) in the outer membrane allow the free diffusion of small molecules and pair with proteins Tom20 and Tom70 which recognize proteins with locator signals and import them through the associated GIP.
How do proteins enter the inner membrane of the mitochondria?
A protein that has a locating sequence for the inner membrane or the matrix will enter the inner membrane through Tim22 or Tim23 gated channels. These channels are very tight to prevent loss of the H+ gradient, thus the folded protein must be denatured (no secondary structure may pass through the port) and pulled through the Tim22 or 23 port. mtHsp70 is an ATPase that binds to the protein and hydrolyzes ATP to pull the protein through the port. Therefor, crossing the inner membrane is ATP dependent, and also requires chaperone proteins to refold the denatured protein.
How do mitochondria fuse and what diseases result from mutations affecting mitochondrial fusion?
Mitochondria do not use SNARE proteins to fuse their membranes, they use mitofusins (Mfn1&2) along with OPA1. Mutations in these proteins cause neuropathies such as autosomal dominant optic atrophy and Chacot-Marie-Tooth. Neuropathies develop because the action of distributing and transmitting neurotransmitters is very energy intensive. Thus, mutations that effect the production of ATP affect neurons sooner than other cells.
What are the oxidized and reduced forms of NADH/NAD+?
NAD+ is the oxidized state NADH is the reduced state NAD functions as a cycler of protons
What are the important steps of glycolysis?
Glucose (6C) is anaerobically converted to pyruvate (3C) producing 2 ATP. Pyruvate may then be reduced to lactic acid (3C). This occurs in the cytosol, NOT in the mitochondria. Yeast may produce ethanol (2C) and CO2 (1C), but only if they are held in anaerobic conditions.
What are the important steps of pyruvate degradation in the mitochondria?
Pyruvate diffuses through the pores in the outer membrane and enters the matrix through a transporter on the inner membrane. In the citric acid/krebs cycle, pyruvate is converted to acetyl coA and produces 3NADH and 1FADH. No ATP is produced in the CAC.
How is the H+ gradient produced?
NADH passes H+ to the cytochromes on the inner membrane. Passage of electrons down the cytochromes pumps 3 H+ out of the matrix. These H+ equilibrate with the cytosol through the pores in the outer membrane, so there is little change in the [H+]outside, but a significant change in [H+] in the matrix. A fourth H+ ion is lost to the creation of H2O inside the matrix as O2 moves across the inner membrane between enzymes III and IV in the electron transport chain.
What is the structure of ATP Synthase?
There is a hexamer of 3 alpha and 3 beta subunits on the matrix side of the inner membrane and a transmembrane domain with H+ channels that cause te structure to rotate. Rotation of the structure causes conformational changes in the alpha subunits. Conformation 1) binding of ADP and Pi, Conformation 2) formation of ATP, Conformation 3) low affinity state of alpha/ATP causes release of ATP. 3H+ used per ATP formed?
How is Cytochrome C involved in apoptosis and how is it activated or inactivated?
When damage is detected, proteins open a pore in the outer membrane that allows cytochrome C to enter into the cytosol and trigger apoptosis pathways if it is oxidated. A cell may stop the apoptosis pathway by reducing cytochrome C in a process that uses ATP. This may have therapeutic potential if cells affected by an MI could be induced to not undergo hypoxia induced apoptosis.
