The Mitochondrial Inner Membrane Protein Mitofilin Controls Cristae Morphology

• DOI: 10.1091/mbc.e04-08-0697
• Publication Date: 2005-01-13T01:24:18Z
• Authors: George B. John; Yonglei Shang; Li Li; Christian Renken; Carmen A. Mannella; Jeanne M.L. Selker; Linda Rangell; Michael J. Bennett; Jiping Zha
• Keywords: Inner membrane; Organelle

Mitochondria are complex organelles with a highly dynamic distribution and internal organization. Here, we demonstrate that mitofilin, previously identified mitochondrial protein of unknown function, controls cristae morphology. Mitofilin is enriched in the narrow space between inner boundary outer membranes, where it forms homotypic interaction assembles into large multimeric complex. Down-regulation mitofilin HeLa cells by using specific small interfering RNA lead to decreased cellular proliferation increased apoptosis, suggesting abnormal function. Although gross fission fusion seemed normal, ultrastructural studies revealed disorganized membrane. Inner membranes failed form tubular or vesicular showed as closely packed stacks membrane sheets fused intermittently, resulting maze membranous network. Electron microscopic tomography estimated substantial increase inner:outer ratio, whereas no junctions were detected. In addition, mitochondria subsequently exhibited reactive oxygen species production potential. metabolic flux due deficiency, oxidative phosphorylation was not accordingly. We propose critical organizer morphology thus indispensable for normal