Cellular Respiration and Mitochondrial Function: Key Concepts and Mechanisms

Key Concepts in Cellular Respiration and Mitochondrial Function

Overview

This study guide summarizes select topics from Chapter 10, focusing on mitochondrial structure, protein import, the citric acid (TCA) cycle, electron transport chain, roles of electron carriers, and the F1F0 ATPase. These are foundational concepts in cell biology, particularly in the context of energy metabolism in eukaryotic cells.

Mitochondrial Structure

Organization and Function

• Mitochondria are double-membraned organelles found in nearly all aerobic eukaryotic cells.

• The outer membrane contains porins, allowing passage of solutes up to 5000 Da.

• The intermembrane space lies between the outer and inner membranes.

• The inner membrane is highly impermeable and forms infoldings called cristae, increasing surface area for electron transport and ATP synthesis.

• The mitochondrial matrix is the innermost compartment, containing enzymes for the TCA cycle and mitochondrial DNA.

• Mitochondria are often clustered in regions of high ATP demand, such as muscle cells.

Mitochondrial Protein Import

Mechanism of Protein Targeting and Translocation

• Most mitochondrial proteins are encoded by nuclear DNA and synthesized in the cytosol.

• Transit sequences at the N-terminus of polypeptides direct proteins to mitochondria.

• Transit peptidase removes the targeting sequence upon entry into the matrix.

• Transport complexes include TOM (Translocase of the Outer Membrane) and TIM (Translocase of the Inner Membrane).

• Chaperone proteins (e.g., Hsp70, Hsp60) maintain polypeptides in an unfolded state for import and assist in proper folding inside the matrix.

The Citric Acid Cycle (TCA/Krebs Cycle)

Oxidative Metabolism of Pyruvate

• In the presence of oxygen, pyruvate is fully oxidized to CO2 via the TCA cycle.

• The cycle begins with the conversion of pyruvate to acetyl CoA by the pyruvate dehydrogenase complex.

• Each round of the cycle releases two CO2 and regenerates oxaloacetate.

• Key products per cycle: 3 NADH, 1 FADH2, 1 GTP (converted to ATP), and 2 CO2.

Overall Reaction:

• $\text{acetyl CoA} + 3\text{NAD}^+ + \text{FAD} + \text{ADP} + P_i \rightarrow 2\text{CO}_2 + 3\text{NADH} + \text{FADH}_2 + \text{CoA-SH} + \text{ATP}$

• Including glycolysis and pyruvate decarboxylation:

• $\text{glucose} + 10\text{NAD}^+ + 2\text{FAD} + 4\text{ADP} + 4P_i \rightarrow 6\text{CO}_2 + 10\text{NADH} + 2\text{FADH}_2 + 4\text{ATP}$

Regulation of the TCA Cycle

• Regulated by allosteric effectors at key enzymes.

• Inhibitors: NADH, ATP, acetyl CoA

• Activators: NAD+, ADP, AMP

• Allosteric regulation ensures metabolic flux matches cellular energy needs.

Electron Transport Chain (ETC)

Electron Flow and Energy Conversion

• Electrons from NADH and FADH2 are transferred to oxygen via a series of protein complexes in the inner mitochondrial membrane.

• The ETC consists of four main complexes (I-IV):

Complex	Function	Protons Pumped
I (NADH dehydrogenase)	Transfers electrons from NADH to CoQ	4
II (Succinate dehydrogenase)	Transfers electrons from succinate to FAD and CoQ	0
III (Cytochrome bc1 complex)	Transfers electrons from CoQ to cytochrome c	4
IV (Cytochrome c oxidase)	Transfers electrons from cytochrome c to O2	2

• Electron transport is coupled to proton pumping, creating a proton gradient across the inner membrane.

• Cytochrome c oxidase (Complex IV) is the terminal oxidase, transferring electrons directly to oxygen.

• Inhibitors such as cyanide and azide block electron transport by binding the Fe-Cu center of cytochrome c oxidase.

Reactive Oxygen Species (ROS)

• Complexes I and III can transfer electrons to oxygen, generating superoxide anion (O2−) or hydrogen peroxide (H2O2).

• ROS contribute to cellular aging and damage; antioxidants neutralize these species.

Electrochemical Proton Gradient and Chemiosmotic Coupling

Mechanism of ATP Synthesis

• The proton gradient generated by the ETC drives ATP synthesis via the F1F0 ATPase (ATP synthase).

• Peter Mitchell's chemiosmotic model (1961) proposed that the electrochemical potential across the membrane links electron transport to ATP formation.

• Each NADH oxidation pumps approximately 10 protons; FADH2 oxidation pumps about 6 protons.

F1F0 ATP Synthase

Structure and Function

• Composed of two main components: F0 (membrane-embedded proton channel) and F1 (catalytic ATP synthesis unit).

• Proton flow through F0 causes rotation of the c-ring and the attached γ subunit, driving conformational changes in F1 for ATP synthesis.

• Binding Change Model (Paul Boyer): Each β subunit cycles through three conformations—Loose (L), Tight (T), and Open (O)—to bind ADP/Pi, synthesize ATP, and release ATP.

ATP Yield Calculations

• Estimated ATP yield per glucose (aerobic respiration): 30-32 ATP (experimentally), 38 ATP (theoretical maximum).

• ATP yield depends on proton gradient utilization and electron shuttle systems for cytosolic NADH.

• Approximate yields:

  • 2.5–3 ATP per NADH

  • 1.5–2 ATP per FADH2

Summary Table: Key Features of Cellular Respiration

Process	Main Location	Key Products
Glycolysis	Cytosol	2 ATP, 2 NADH, 2 Pyruvate
TCA Cycle	Mitochondrial Matrix	2 ATP (GTP), 6 NADH, 2 FADH2, 4 CO2
Electron Transport Chain	Inner Mitochondrial Membrane	Proton gradient, H2O
ATP Synthesis	Inner Mitochondrial Membrane (F1F0 ATPase)	~30-32 ATP per glucose

Example: Allosteric Regulation in Glycolysis

• Phosphofructokinase-1 (PFK-1) is a key regulated enzyme in glycolysis.

• Allosteric inhibitors: ATP, citrate

• Allosteric activators: AMP, ADP, fructose-2,6-bisphosphate

• Regulation ensures glycolytic flux matches cellular energy demand.

Additional info: The Nobel Prize slides are not directly relevant to cell biology but are included as context for scientific achievement. The main content is focused on cellular respiration and mitochondrial function, which are core topics in cell biology.