A 46-year-old Caucasian male presents to your office with a slowly growing neck mass. The mass is stony hard on palpation and seems to be fixed to the adjacent tissues. After initial evaluation, combination chemotherapy is prescribed to the patient. Several weeks later the mass significantly decreases in size, and biopsy demonstrates many shrunken eosinophilic cells within the tumor. Which of the following substances released from mitochondria most likely triggered the observed cellular changes?

Question

A 46-year-old Caucasian male presents to your office with a slowly growing neck mass.  The mass is stony hard on palpation and seems to be fixed to the adjacent tissues.  After initial evaluation, combination chemotherapy is prescribed to the patient.  Several weeks later the mass significantly decreases in size, and biopsy demonstrates many shrunken eosinophilic cells within the tumor.  Which of the following substances released from mitochondria most likely triggered the observed cellular changes?

Quizplus · Accepted Answer

Apoptosis is a means of carefully regulated cell death in which the cell activates enzymes to degrade its own nuclear DNA and proteins. Although the cell membrane remains intact during apoptosis, the cell becomes an appealing target for phagocytosis. Because no cell contents are leaked into the surrounding tissue, there is no associated inflammation. The process of apoptosis is separated into an initiation phase and an execution phase. During the initiation phase, protein-hydrolyzing caspases are activated. In the execution phase, these caspases bring about the cell death by cleaving cellular proteins and activating DNAses. The initiation of apoptosis occurs via signals from two separate pathways: the intrinsic (mitochondrial) pathway and the extrinsic (death receptor) pathway. In the intrinsic pathway, the mitochondria become more permeable and pro-apoptotic substances are released into the cytoplasm in response to stress or the cessation of survival signals. Once the cell is exposed to stress or the cessation of survival signals, the anti-apoptotic proteins Bcl-2 and Bcl-x that reside in the mitochondrial membranes and cytoplasm are replaced with pro-apoptotic proteins such as Bak, Bax, and Bim. The pro-apoptotic proteins allow for the increased permeability of the mitochondria, which results in the release of caspase-activating substances like cytochrome c. (Choice A) Hemosiderin accumulation is common in patients who have hemolytic anemia or who undergo frequent blood transfusions. It is not associated with apoptosis. (Choice B) The extrinsic pathway requires engagement of death receptors on the cell surface. These death receptors are in the tumor necrosis factor receptor family, with the type 1 TNF receptor (TNFR1) and a related protein named Fas (CD95) the two best known members of this family. After cross-linkage of Fas with its ligand, multiple molecules of Fas come together to form a binding site for a death-domain containing adapter protein called FADD. FADD then binds an inactive form of a caspase, again bringing multiple caspase proteins together that through a cascade effect eventually induce caspase activation. (Choice D) Succinate dehydrogenase is a mitochondrial enzyme in the electron transport chain that acts by oxidizing succinate into fumarate and reducing FAD to FADH₂. This enzyme is not involved in apoptosis. (Choice E) Superoxide dismutase catalyzes the reduction of superoxide anions to hydrogen peroxide. This enzyme is not involved in apoptosis. (Choice F) Lipoxygenase plays a key role in the synthesis of leukotrienes, a class of inflammatory mediators. Educational Objective: Cytochrome c is a mitochondrial enzyme that activates caspases and indirectly brings about cell death through intrinsic pathway apoptosis.

A 46-Year-Old Caucasian Male Presents to Your Office with a Slowly