Ground control to major TOM: mitochondria-nucleus communication.
Mitochondria have crucial functions in the cell, including ATP generation, iron-sulfur cluster biogenesis, nucleotide biosynthesis, and amino acid metabolism. All of these functions require tight regulation on mitochondrial activity and homeostasis. As mitochondria biogenesis is controlled by the nucleus and almost all mitochondrial proteins are encoded by nuclear genes, a tight communication network between mitochondria and the nucleus has evolved, which includes signaling cascades, proteins which are dual-localized to the two compartments, and sensing of mitochondrial products by nuclear proteins. All of these enable a crosstalk between mitochondria and the nucleus that allows the 'ground control' to get information on mitochondria's status. Such information facilitates the creation of a cellular balance of mitochondrial status with energetic needs. This communication also allows a transcriptional response in case mitochondrial function is impaired aimed to restore mitochondrial homeostasis. As mitochondrial dysfunction is related to a growing number of genetic diseases as well as neurodegenerative conditions and aging, elucidating the mechanisms governing the mitochondrial/nuclear communication should progress a better understanding of mitochondrial dysfunctions.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Michal
M
Eisenberg-Bord
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Maya
M
Schuldiner
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001678:Organelle Biogenesis; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D056811:Unfolded Protein Response
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011956:Receptors, Cell Surface; C084008:TOMM20 protein, human; D000255:Adenosine Triphosphate
communication; dual targeting; mitochondria; nucleus; signaling pathways