Decoding and influencing mitochondrial inner membrane ultra-structure biogenesis

Mukherjee, Indrani

dc.contributor.advisor	Meinecke, Michael Prof. Dr.
dc.contributor.author	Mukherjee, Indrani
dc.date.accessioned	2022-04-28T13:50:42Z
dc.date.available	2022-05-05T00:50:10Z
dc.date.issued	2022-04-28
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14022
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-9214
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc	572	de
dc.title	Decoding and influencing mitochondrial inner membrane ultra-structure biogenesis	de
dc.type	doctoralThesis	de
dc.contributor.referee	Meinecke, Michael Prof. Dr.
dc.date.examination	2021-12-08	de
dc.description.abstracteng	The Mitochondrion is a ubiquitous organelle known to be involved in a variety of vital cellular functions besides its central role in ATP synthesis such as, cellular metabolism, signalling and apoptosis. Dynamic in both structure and function, mitochondria have two membranes wherein the outer membrane (OM) is flat essentially forming a border and separating them from the rest of the cell, while the inner membrane (IM) is highly folded. The IM is further subdivided into the inner boundary membrane (IBM) that is rather flat, cristae membranes (CM) which can be flat (lamellar cristae) or curved (tubular cristae) as well as the cristae junctions (CJ) and cristae rims (CR), both exhibiting a high degree of membrane curvature. The CJ are narrow tubular membrane segments in the IM joining the IBM and CM. Recent studies have shown that the conserved multi-subunit MICOS complex (mitochondrial contact site and cristae organizing system) is localized at the CJ and differences in the expression levels of its sub-units lead to drastic alterations in the IM morphology. MICOS mainly consists of integral membrane proteins where Mic10 is one of the core subunits and is required for bending the membrane at CJ. Mic60 is the second MICOS core component and carries out both, maintenance of CJ as well as protein-protein interactions. Previous studies have shown that deletion of Mic10 or Mic60 results in the accumulation of membrane stacks in the mitochondrial matrix. Furthermore, it has been previously proven that Mic10 consists of highly conserved glycine rich motifs in both of its transmembrane domains which enables its homo-oligomerization essential for maintaining cristae morphology at CJ. In this study, we investigated the role of Mic10 in maintaining proper morphology at CJ via homo-oligomerization. An in vitro approach was used wherein, short peptides mimicking either of the two transmembrane domains of Mic10, including the GxGxG motifs were added to the purified wild type protein. We observed that the peptides greatly influence the oligomerization pattern of Mic10. Additionally, in vivo cell culture methods were employed to generate Mic10 and Mic60 KD/KO cells to analyze its effect on the mitochondrial cristae morphology and physiological processes. We showed that both MIC10 and MIC60 depletion can cause aberrant cristae morphology, reduced mitochondrial respiration capacity, lowered mitochondrial ROS levels as well as decreased cellular proliferation in all cell types investigated. Interestingly, these effects were stronger in MIC60 KD/KO cells as compared to MIC10 KD/KO or WT cells. Therefore, the present study provides evidence to suggest that MIC60 is a more crucial core sub-unit of the MICOS complex required to maintain mitochondrial homeostasis and regulate proper signalling	de
dc.contributor.coReferee	Schwappach, Blanche Prof. Dr.
dc.subject.eng	membrane biochemistry	de
dc.subject.eng	mitochondrial biology	de
dc.subject.eng	mitochondrial physiology	de
dc.subject.eng	MICOS	de
dc.subject.eng	yeast	de
dc.subject.eng	mammalian cells	de
dc.subject.eng	protein biochemistry	de
dc.subject.eng	molecular biology	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-14022-9
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.description.embargoed	2022-05-05	de
dc.identifier.ppn	1800601271

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1114]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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