protein import in mitochondria 2

What provides the main driving forces for mitochondrial protein import?

ATP hydrolysis and the electrochemical membrane potential (Δψ)

What keeps cytosolic mitochondrial precursor proteins unfolded?

Cytosolic Hsp70 using ATP

What is the charge distribution across the inner mitochondrial membrane?

IMS positive and matrix negative

Which complex imports almost all mitochondrial proteins first?

TOM complex

Which inner-membrane translocase handles presequence-containing proteins?

TIM23 complex

What two factors pull presequences into the matrix?

Δψ and mtHsp70 ATP-driven binding

Which model of mtHsp70 explains binding without pulling?

Brownian ratchet model

Which model suggests mtHsp70 physically pulls the polypeptide?

Power stroke model

What complex anchors mtHsp70 for the power stroke?

PAM complex

What is a stop-transfer sequence?

A hydrophobic α-helix that halts translocation and triggers lateral membrane insertion

Which complex laterally opens to insert inner-membrane helices?

TIM23

What does Mgr2 regulate?

Gatekeeping of which proteins laterally insert into the inner membrane

What happens when Mgr2 is overexpressed?

Inner-membrane insertion is blocked

What happens when Mgr2 is deleted?

Proteins insert into the inner membrane even when they shouldn’t

What mechanism did Sim et al. (2023) propose for stop-transfer insertion?

Stop-transfer triggers Mgr2 release and opens a gap for membrane insertion

Which complex inserts proteins from the matrix side into the inner membrane?

OXA1 complex

Where do OXA substrates first accumulate?

The mitochondrial matrix

Why are OXA substrates typically encoded by mtDNA or fully imported first?

They contain multiple hydrophobic helices that would aggregate in the cytosol

What pathway inserts IMS proteins that become soluble?

Membrane insertion followed by cleavage in the IMS

Which pathway handles mitochondrial carrier proteins?

The TIM22 pathway

How many transmembrane helices do most carrier proteins have?

Six

Why do carrier proteins need small Tim chaperones?

They are highly hydrophobic and prone to aggregation

Do carrier proteins fully enter the IMS?

No

What drives TIM22 insertion?

The membrane potential (Δψ)

What experiment revealed the loop model for TIM22 insertion?

DHFR fusion experiments with methotrexate block

Why does DHFR block import?

Folded DHFR cannot pass through TOM

What distinguishes matrix-targeted proteins in crosslink studies?

They bind acidic patches like Psu9 via positively charged presequences

What environment in the IMS allows small Tims to fold stably?

An oxidizing environment

Why can small Tims not exit after folding?

Disulfide bonds make them too large to pass back through TOM

Which complex inserts β-barrel proteins into the outer membrane?

SAM complex

Which chaperones help β-barrels before SAM insertion?

Small Tim proteins

What type of membrane proteins does SAM recognize?

β-barrel proteins lacking classical hydrophobic helices