Senior Honors Theses

Publication Date

Spring 4-22-2013

School

College of Arts and Sciences

Major

Biology: Pre-Med

Primary Subject Area

Biology, Cell; Biology, Molecular; Biology, Physiology

Keywords

Apoptosis, Cytochrome C, Mitochondria

Disciplines

Cell Biology | Cellular and Molecular Physiology | Systems and Integrative Physiology

Abstract

A cell may use one of three main apoptotic pathways leading to programmed cell death: the extrinsic pathway, the perforin/granzyme pathway and the intrinsic pathway. The most pertinent to this discussion is the intrinsic pathway, which utilizes the mitochondria as an essential intermediary. Mitochondria’s primary function in relation to this pathway is the subsequent release of pro-apoptotic factors including cytochrome c, which activate a caspase cascade leading to the death of the cell. Cytochrome c is released partly due to an increase in cytosolic calcium levels. Two methods of the release of cytochrome c have been proposed. The first is through permeability transition pores (PTP) in the inner mitochondrial membrane, which result in the rupturing of the mitochondria and the subsequent release of inner membrane space proteins. The second method is through mitochondrial apoptosis-induced channels (MAC) in the outer membrane, which maintains the integrity of the mitochondria. Murine brain and liver mitochondria were incubated with various concentrations of calcium and a subsequent western blot for cytochrome c was performed. It appears that an increase in calcium concentration induces a higher level of cytochrome c release in liver mitochondria providing stronger evidence for the MAC pathway. Brain mitochondria did not express a calcium dosage response providing evidence for the PTP pathway.

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