mitochondria Flashcards
what is the mitochodndria
organelle that generates metabolic energy (ATP)
- contain their own genome (semi-autonomous)
- replication is controlled by both the cell (nuclear genome) and the organelle genome itself
- arise only from pre-existing mitochondria
mitochondria structure
double-membrane bound organelle
- inner membrane
- outer membrane
-intermembrane space
- matrix
mitocondria outer membrane
- permeable to ions and small molecules
- contains porins: integral membrane proteins with a large inner channel
mitochondria inner membrane
- lies adjacent to outer membrane
- forms folds (cristae) that extend to interior
- impermeable - IMS has high [H+], maintains [H+] gradient
- site of ATP synthase
mitochondrial matrix
aqueous interior
- site of TCA cycle, ATP for oxidative phosphorylation
- contains mitochondrial genome
- contains ribosomes - used for translation of mitochondrial gene-encoded proteins
mitochondrial network
highly branched, long interconnected series of tubules
- allows for cell-wide co-orientation of organelle functioning and biogenesis
- tubules are mobile and can fuse with one another and/or split apart (fission)
- defective mitochondrial networks correlate with neurodegenerative diseases
when does mitochondrial fission happen
- at the end of G1 during cell death (apoptosis)
- rates of fission vs fusion control the number and size of the mitochondrial network
when does mitochondrial fusion occur
- in response to cell stress (if energy is required)
- involves mitochondrial membrane proteins, GTP and remodelling of membrane lipids
steps in mitochondrial fusion
- outer membrane tethering
- Mfn1 and Mfn2 on adjacent mitochondria dimerize in a GTP-dependent manner to form the organelle tethering complex - regulated by Bax - outer membrane fusion
- at the site of Mfn1/2 tethering phospholipase D converts cardiolipin into phosphatidic acid, this causes the outer membrane to curve inward and to fuse - inner membrane fusion
- mediated by OPA1 - OPA1 proteins on adjacent inner membranes interact in a GTP-dependent manner to promote membrane fusion - OPA binding regulated by prohibitin
steps in mitochondrial fission
- assembly of the Drp1 ring
- Fis1 is recruited to lipid micro-domains that form the scission site
- Fis1 in conduction with MiD and Mff recruit Drp1 to form a ring around the outer membrane (like dynamin) - mitochondrial scission
- Drp1 is a G-protein bound to GTP during ring formation
- hydrolysis of GTP causes the Drp1 ring to constrict and scission to occur
how does a cell ensure a nascent protein is targeted to the correct sub-compartment of the mitochondria
- all mitochondrial proteins posses unique targeting sequences
- sequences mediate protein targeting from cytosol to mitochondria and then to a specific sub-compartment
*Targeting and import of matrix proteins
- protein is recognized in the cytosol by Hsp70, Hsp70 maintains a partially unfolded competent state using ATP
- at the surface of the mitochondria, the proteins N-terminus targeting sequence is recognized by the TOM 20/22 dimer (acts as a receptor buck lacks a channel)
- TOM20/22 passes the matrix targeting sequence and passes it to TOM 40 which has a channel to the IMS
- the protein is passed from TOM40 to the TIM complex which form a channel through the inner membrane
- the positively charged matrix targeting sequence is attracted to the less positive matrix
- as the N-terminal sequence exits the TIM channel it binds to the chaperon mtHsp70
- the matrix targeting sequence is cleaved by MPP and mtHsp70 and other chaperons help with proper protein folding
mitochondria membrane import complexes
TOM20/22: import receptor complex on the outer membrane, lacks a channel
TOM40: general import pore of the outer membrane
TIM23/17: inner membrane channel
- all are translocases
electrochemical potential in the mitochondria
[H+] IMS > [H+] matrix
what do the 3 inner membrane targeting and import pathways all have in common
- 3 separate pathways that all utilize TOM40 to cross the outer membrane
IM targeting and import path A
- at the mitochondria surface, the IMPs N-terminus has a matrix-targeting sequence which is recognized by TOM20/22
- the targeting sequences enters the IMS by TOM40 and the targeting sequence is passed to the TIM complex
- the N-terminus moves into the matrix utilizing the proton gradient
- the matrix targeting sequence is cleaved but the protein is not pulled all the way to the matrix - due to hydrophobic alpha-helix that acts as a stop-transfer anchor sequence
- TIM has a lateral gate that allows the TMD to enter the inner membrane bilayer
IM targeting and import path B
- proteins translocate to the matrix FIRST in the same manner as soluble matrix proteins
- these proteins possess an Oxa1-targeting sequence
- the Oxa-1 sequence directs the protein to the Oxa-1 protein which in turn, embeds the protein into the inner membrane
IM targeting and import path C
- these proteins DO NOT have a matrix-targeting sequence
- instead they have internal targeting sequences which will be the hydrophobic TMDs
- TOM70 recognizes these internal targeting sequences and directs the protein through TOM40
- TIM 9 and 10 are responsible for moving the protein to a TIM22/54 dimer which embeds the protein in the IMM
inter membrane space targeting and import
- soluble matrix proteins contain a intermembrane-space-targeting sequence (TMD) that embeds them into the IMM
- the IMS targeting sequence is identical to the STA sequence used by IMPs in path A
- once embedded into the membrane, a protease cleaves the protein on the IMS side of the inner membrane
- the TMD will be degraded
- the soluble portion of the protein will now properly fold
