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MCB 2050 second half > mitochondria > Flashcards

mitochondria Flashcards

1
Q

what is the mitochodndria

A

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

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2
Q

mitochondria structure

A

double-membrane bound organelle
- inner membrane
- outer membrane
-intermembrane space
- matrix

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3
Q

mitocondria outer membrane

A
  • permeable to ions and small molecules
  • contains porins: integral membrane proteins with a large inner channel
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4
Q

mitochondria inner membrane

A
  • lies adjacent to outer membrane
  • forms folds (cristae) that extend to interior
  • impermeable - IMS has high [H+], maintains [H+] gradient
  • site of ATP synthase
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5
Q

mitochondrial matrix

A

aqueous interior
- site of TCA cycle, ATP for oxidative phosphorylation
- contains mitochondrial genome
- contains ribosomes - used for translation of mitochondrial gene-encoded proteins

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6
Q

mitochondrial network

A

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

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7
Q

when does mitochondrial fission happen

A
  • at the end of G1 during cell death (apoptosis)
  • rates of fission vs fusion control the number and size of the mitochondrial network
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8
Q

when does mitochondrial fusion occur

A
  • in response to cell stress (if energy is required)
  • involves mitochondrial membrane proteins, GTP and remodelling of membrane lipids
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9
Q

steps in mitochondrial fusion

A
  1. outer membrane tethering
    - Mfn1 and Mfn2 on adjacent mitochondria dimerize in a GTP-dependent manner to form the organelle tethering complex - regulated by Bax
  2. 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
  3. 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
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10
Q

steps in mitochondrial fission

A
  1. 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)
  2. 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
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11
Q

how does a cell ensure a nascent protein is targeted to the correct sub-compartment of the mitochondria

A
  • all mitochondrial proteins posses unique targeting sequences
  • sequences mediate protein targeting from cytosol to mitochondria and then to a specific sub-compartment
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12
Q

*Targeting and import of matrix proteins

A
  • 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
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13
Q

mitochondria membrane import complexes

A

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

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14
Q

electrochemical potential in the mitochondria

A

[H+] IMS > [H+] matrix

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15
Q

what do the 3 inner membrane targeting and import pathways all have in common

A
  • 3 separate pathways that all utilize TOM40 to cross the outer membrane
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16
Q

IM targeting and import path A

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
17
Q

IM targeting and import path B

A
  • 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
18
Q

IM targeting and import path C

A
  • 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
19
Q

inter membrane space targeting and import

A
  • 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

MCB 2050 second half (6 decks)

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