EXPLORING ASSEMBLY &FUNCTION OF CAF4 COMPLEX & ITS ROLE IN MITOCHONDRIAL FISSION

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mitochondria are the powerhouse of the cell, producing the bulk of the ATP energy necessary for cellular function. The production of this ATP energy is dependent upon the maintenance of a specialized mitochondrial structure. Textbooks often simplistically present this structure to look like a jelly bean; however, mitochondria are actually tubular and highly branched. This specialized tubular structure is maintained by complementary fusion and fission events during which two mitochondria merge into one, or one mitochondrion divides into two, respectively. These events must be balanced because too much of either fission or fusion can alter the structure of the mitochondria, potentially resulting in loss of function and leading to diseases such as dominant optic atrophy, a disease causing childhood blindness. To understand the regulation of mitochondrial structure this project focuses on a recently identified protein  Caf4  and its role in mitochondrial fission. Three proteins, Dnm1, Mdv1, and Fis1 mediate the physical division of the mitochondrial tubule. While some of the steps that take place to mediate the actual division event are well understood, it is not known what instructs the mitochondria to divide. We hypothesize that Caf4 may transmit this signal or instruction to the other proteins. Using fluorescent microscopy we propose to determine Caf4's function in mitochondrial division, specifically determining if Caf4 instructs Dnm1, Mdv1, and Fis1 to activate. Understanding Caf4's function in mitochondrial division will provide valuable insight into how the regulation of mitochondrial structure affects mitochondrial function and, in turn, help us understand mitochondrial diseases.