Metabolic: lecture 22

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Questions and Answers

What is the primary role of anaplerotic reactions in the citric acid cycle?

To facilitate the oxidation of fatty acids.

To transport reducing power across mitochondrial membranes.

To replenish intermediates used in biosynthetic pathways. (correct)

To break down carbohydrates for energy production.

Which shuttle is primarily responsible for transferring reducing power (NADH) into the mitochondria?

Lactate shuttle

Glycolytic shuttle

Glycerol-3-phosphate shuttle

Malate-aspartate shuttle (correct)

Which of the following is NOT a characteristic of the glycerol-3-phosphate shuttle?

It operates primarily in skeletal muscle and brain.

It is bound to the outer face of the inner mitochondrial membrane.

It transfers reducing power from mitochondria to the cytosol. (correct)

It does not involve membrane transport systems.

Which statement about CAC intermediates is true concerning their role in metabolism?

They support both degradative and biosynthetic metabolism. Signup and view all the answers

What is the function of the malate-ketoglutarate transporter in mitochondria?

To transfer intermediates and reducing powers in and out of mitochondria. Signup and view all the answers

What is the primary source of most mitochondrial proteins?

Cytoplasmic ribosomes Signup and view all the answers

Which component is essential for the initial step of mitochondrial protein import?

TOM Signup and view all the answers

What is the function of the targeting signal identified in mitochondrial proteins?

It serves as a 'postal address' for the protein's destination Signup and view all the answers

Which system is involved in the assembly of β-barrel proteins in the outer mitochondrial membrane?

SAM Signup and view all the answers

What role does MIA play in mitochondrial protein import?

It assists in the import of soluble IMS proteins Signup and view all the answers

Which mitochondrial location is targeted by the TIM translocon?

Mitochondrial matrix Signup and view all the answers

What is the characteristic structure of the targeting sequence of mitochondrial proteins?

Amphipathic helix with positive and uncharged residues Signup and view all the answers

Which of the following is NOT a mitochondrial protein import mechanism?

ROM Signup and view all the answers

Study Notes

Interactions Between Mitochondria and the Surrounding Cell

Metabolic interactions are a key aspect of mitochondrial function
Protein import is crucial for mitochondrial function.
Genetic interactions between mitochondria and the surrounding cell will be covered in a later lecture.

Krebs Cycle Intermediates

Krebs cycle intermediates have both catabolic and anabolic roles.
These intermediates participate in both degradation and synthesis of molecules.
Red arrows illustrate anaplerotic reactions, replenishing intermediates as they leave the cycle.
Gluconeogenesis uses these intermediates (e.g., oxaloacetate).
Replenishing oxaloacetate is a crucial aspect of the cycle.

Anaplerotic Reactions

Intermediates in the citric acid cycle (CAC) are used for biosynthetic pathways.
These intermediates need to be replenished to maintain a functioning cycle.
Four-carbon intermediates are formed by carboxylation of three-carbon precursors (e.g., pyruvate).
Several reactions replenish oxaloacetate, using different enzymes and tissues/organisms. (e.g., pyruvate carboxylase in liver and kidney).

Transfer of Metabolites and Reducing Power

Mitochondria are impermeable to NADH.
Metabolite shuttles are needed for NADH transport.
Shuttles (e.g., malate-aspartate shuttle) enable indirect NADH transfer across the mitochondrial membrane.
Transamination and metabolite transporters are essential for moving metabolites in and out of the mitochondria.

Malate-Aspartate Shuttle

This shuttle transfers reducing power (NADH) between the cytosol and the mitochondrial matrix.
Oxaloacetate and glutamate are crucial intermediate in this shuttle.
Aminotransferases (AAT) are involved in the transfer of amino groups.
The shuttle operates in response to the demand for NADH within the mitochondria.

Glycerol-3-Phosphate Shuttle

This method of transferring NADH is used in skeletal muscle and brain.
The shuttle employs glycerol-3-phosphate dehydrogenase and involves FAD.
The shuttle does not cross the mitochondrial inner membrane and thus does not require transporters.

IMM Transporters

Outer mitochondrial membrane is generally permeable to most small molecules.
Important pathways such as gluconeogenesis require transport of metabolites like oxaloacetate in or out of the mitochondria.
Malate and Citrate may be transported.
ATP-ADP translocase, Dicarboxylic acid carrier, Tricarboxylate carrier and Phosphate carrier are key examples of transporters.

Mitochondrial Proteins

Many mitochondrial proteins are encoded by nuclear DNA.
These proteins are synthesized on cytoplasmic ribosomes and then targeted to the four mitochondrial compartments.
Different locations such as outer membrane, inner membrane, intermembrane space, and matrix space need different transport and targeting mechanisms.
19% of mitochondrial proteins' functions are still unknown and require further investigation.

Mitochondrial Protein Import

Proteins destined for mitochondria are initially synthesised in the cytoplasm.
Post-translational targeting mechanism.
Proteins possess an N-terminal signal sequence (transit peptide) that acts as a "postal address".
This signal targets the nascent protein to mitochondrial membranes.
Receptor proteins (e.g., TOM complex) on the mitochondrial surface bind to the signal sequence to guide the protein import.

In Vitro Import of Nuclear-Encoded Proteins

Studying how proteins are transported using in vitro assays.
Experiments verify the effectiveness of proteins’ import with/without using a protease.

Mitochondrial Protein Import Mechanisms

TOM (Translocase of the outer membrane) plays a vital initial step in targeting proteins.
TOM reads the N-terminal signal sequence that enables it to direct the protein to the right location.
Other factors (e.g., TIMs, SAMs) and other proteins are involved.

Mitochondrial Protein Import and Assembly Machinery

Proteins destined for the mitochondria are imported post-translationally.
TOM, TIM, SAM, and MIA are important players in this process.

Targeting Metabolite Carriers

These carriers can be targeted to specific locations.
TIM22 and TIM23, are involved in targeting to the inner membrane.
Chaperones and further specialized protein machinery play vital roles.

Soluble IMS and Matrix Protein Import

Complex systems are engaged to transfer soluble proteins to the IMS and Matrix of the mitochondria from cytosol.
These proteins need various proteins like Mia (Mitochondrial Import and Assembly system) for transportation.

Mitochondrial Import of Nuclear-Encoded Proteins

Nuclear-encoded proteins (that are involved in mitochondrial functions) require import into mitochondrial compartments.
Different import pathways exist for small IMS proteins and other proteins.
Specialized machinery (e.g., PAM, TIMs) are involved in transporting these proteins, and sorting and assembly machinery (SAM) are also engaged.

Mitochondrial DNA (mtDNA)

Mitochondrial DNA is circular and conserved.
The genome contains 37 genes, including those necessary for oxidative phosphorylation.
Most mitochondrial proteins that are required are encoded by nuclear DNA.

Oxidase Assembly Translocase (Oxa)

Oxa helps nuclear-encoded inner membrane proteins to connect with mitochondrial-encoded proteins.
Proteins that require Oxa are identified by specific sequences on the protein.

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Description

This quiz covers the interactions between mitochondria and surrounding cells, focusing on metabolic functions and protein import. It further explores the role of Krebs cycle intermediates in both catabolism and anabolism, including their replenishment through anaplerotic reactions. Test your knowledge on these crucial biochemical processes.