Description
Mitochondrial dynamics and cellular iron homeostasis
Atsushi Tanaka1, Hiroaki Inoue1, Sevan Mattie2, Heidi McBride2
1Res. Inst. of Med. Sci., Yamagata Univ., 2Montreal Neuro. Inst., McGill Univ
e-mail: atsushi.tanaka@med.id.yamagata-u.ac.jp
Mitochondria has been well understood as eukaryotic organelle producing cellular energy. Recent studies on mitochondria have demonstrated that they actively communicate with other cellular organelles to maintain function, dynamics, and biogenesis.
We recently investigated how mitochondria send information to other organelles or receive it from them to change their function and dynamics. In a human neuroblastoma cell line, SH-SY5Y, mitochondrial-derived vesicles (MDVs) are formed in response to interference with iron metabolism. These iron-stress induced MDVs show unique structures and dynamics that is distinct from other stress, such as oxidative stress induced MDVs. During the formation of iron-stress induced MDVs, mitochondria recruit endo-/ lysosomes to sites of budding MDVs; MDVs are then formed from the body of mitochondria. Upon the formation of MDVs, this inter-organelle contacts likely create sites for transfer of mitochondrial granules to endo-/ lysosomes via MDVs. Interestingly, this event does not require canonical autophagy system, such as isolation membrane formation onto mitochondrial membrane, or sequestration by autophagosome structures, however, it requires lysosomal or proteasomal function. These observations indicated that mitochondria sense cellular iron homeostasis and cooperate with endo-/ lysosomes and other cellular machineries to respond to the change of iron metabolism. This may produce an effective stress response during interfere of iron metabolism. Once this novel vesicle formation mechanism is disrupted, dysregulation of iron dynamics might be exacerbated by the abnormal iron distribution in a cell, and then linked to pathogenic condition. In this symposium, we will discuss physiological function of mitochondria-endo-/ lysosome contact sites, which contain the platform of mitochondrial vesicle formation.
Keywords: mitochondria, lysosome, iron, dynamics, vesicles