A small GTPase involved in mitochondrial morphology and function

2015 ◽  
Vol 43 (1) ◽  
pp. 108-110 ◽  
Author(s):  
Anne Spang
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Complex ◽  
Essential Role ◽  
Small Gtpase ◽  
Mitochondrial Morphology ◽  
Interconnected Network ◽  
Contact Sites ◽  
Close Proximity ◽  
And Function ◽  
Adp Ribosylation Factor

Mitochondria are the powerhouse of cells as they produce the bulk of ATP which is consumed by the cell. They form a highly interconnected network that is governed by fission and fusion processes. In addition, mitochondria and the endoplasmic reticulum (ER) are found in close proximity to each other and it is thought that they maintain contact sites to exchange molecules. The regulation and the function of these contact sites need to be further explored. The small GTPase Arf1 (ADP-ribosylation factor 1), which is best known for its essential role in the generation of coatomer protein I (COPI)-coated vesicles at the Golgi complex appears to be also essential for the dynamics and maintenance of mitochondrial function, presumably at ER–mitochondrial contact sites.

New horizons in mitochondrial contact site research

2020 ◽  
Vol 401 (6-7) ◽  
pp. 793-809
Author(s):  
Naama Zung ◽  
Maya Schuldiner
Keyword(s):  
Endoplasmic Reticulum ◽  
Molecular Mechanisms ◽  
Contact Site ◽  
New Horizons ◽  
Contact Sites ◽  
Future Goals ◽  
Close Proximity ◽  
Recent Developments ◽  
Site Field ◽  
First Contact

AbstractContact sites, areas where two organelles are held in close proximity through the action of molecular tethers, enable non-vesicular communication between compartments. Mitochondria have been center stage in the contact site field since the discovery of the first contact between mitochondria and the endoplasmic reticulum (ER) over 60 years ago. However, only now, in the last decade, has there been a burst of discoveries regarding contact site biology in general and mitochondrial contacts specifically. The number and types of characterized contacts increased dramatically, new molecular mechanisms enabling contact formation were discovered, additional unexpected functions for contacts were shown, and their roles in cellular and organismal physiology were emphasized. Here, we focus on mitochondria as we highlight the most recent developments, future goals and unresolved questions in the field.

scholarly journals RAB6 and microtubules restrict protein secretion to focal adhesions

2019 ◽  
Vol 218 (7) ◽  
pp. 2215-2231 ◽  
Author(s):  
Lou Fourriere ◽  
Amal Kasri ◽  
Nelly Gareil ◽  
Sabine Bardin ◽  
Hugo Bousquet ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Cell Surface ◽  
Protein Secretion ◽  
Golgi Complex ◽  
Essential Role ◽  
Focal Adhesions ◽  
Secreted Proteins ◽  
Cell Compartments ◽  
Secretion Assay

To ensure their homeostasis and sustain differentiated functions, cells continuously transport diverse cargos to various cell compartments and in particular to the cell surface. Secreted proteins are transported along intracellular routes from the endoplasmic reticulum through the Golgi complex before reaching the plasma membrane along microtubule tracks. Using a synchronized secretion assay, we report here that exocytosis does not occur randomly at the cell surface but on localized hotspots juxtaposed to focal adhesions. Although microtubules are involved, the RAB6-dependent machinery plays an essential role. We observed that, irrespective of the transported cargos, most post-Golgi carriers are positive for RAB6 and that its inactivation leads to a broad reduction of protein secretion. RAB6 may thus be a general regulator of post-Golgi secretion.

scholarly journals Requirement for Neo1p in Retrograde Transport from the Golgi Complex to the Endoplasmic Reticulum

2003 ◽  
Vol 14 (12) ◽  
pp. 4971-4983 ◽  
Author(s):  
Zhaolin Hua ◽  
Todd R. Graham
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Complex ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Retrograde Transport ◽  
Transport Pathway ◽  
Transport Defect ◽  
Copii Vesicles ◽  
P Type ◽  
Adp Ribosylation Factor

Neo1p from Saccharomyces cerevisiae is an essential P-type ATPase and potential aminophospholipid translocase (flippase) in the Drs2p family. We have previously implicated Drs2p in protein transport steps in the late secretory pathway requiring ADP-ribosylation factor (ARF) and clathrin. Here, we present evidence that epitope-tagged Neo1p localizes to the endoplasmic reticulum (ER) and Golgi complex and is required for a retrograde transport pathway between these organelles. Using conditional alleles of NEO1, we find that loss of Neo1p function causes cargo-specific defects in anterograde protein transport early in the secretory pathway and perturbs glycosylation in the Golgi complex. Rer1-GFP, a protein that cycles between the ER and Golgi complex in COPI and COPII vesicles, is mislocalized to the vacuole in neo1-ts at the nonpermissive temperature. These phenotypes suggest that the anterograde protein transport defect is a secondary consequence of a defect in a COPI-dependent retrograde pathway. We propose that loss of lipid asymmetry in the cis Golgi perturbs retrograde protein transport to the ER.

Evidence for Golgi Origin of Melanosomes

1968 ◽  
Vol 26 ◽  
pp. 148-149
Author(s):  
Gerd G. Maul
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Golgi Apparatus ◽  
Golgi Complex ◽  
Serial Sections ◽  
Human Malignant Melanoma ◽  
Close Proximity ◽  
Membrane Bound ◽  
Tubular Endoplasmic Reticulum ◽  
Internal Architecture

Electron microscopy has provided evidence that the melanosome evolves as a membrane bound structure with a highly complex internal architecture. The premelanosomes are found in close proximity to the golgi apparatus. Therefore, it was generally agreed that the melanosomes originate from the golgi apparatus.Vesicles have been described to pinch off the cysternae of the golgi apparatus. The vesicles would then grow and acquire a dense material. This material is aggregating to form the characteristic helical strands onto which melanin is deposited. Cloned human malignant melanoma lines were used to reinvestigate the problem of melanosome formation. The reconstruction of serial sections revealed the arrangement of premelanosomes and melanosomes in relation to the golgi complex. This study demonstrated that premelanosomes and melanosomes are continuous with the golgi complex by a smooth-surfaced tubular endoplasmic reticulum (SER) (Fig. la-d). The continuity of membranes of the SER and the premelanosome is depicted in Fig. 2. In this early premelanosome the protein strands have not yet coiled up into a helix. Rough-surfaced endoplasmic reticulum (RER) was also observed to be continuous with the golgi apparatus and melanosomes. After melanogenesis has started (Fig. 3) small vesicles appear inside the premelanosomes.

scholarly journals Analysis of De Novo Golgi Complex Formation after Enzyme-based Inactivation

2007 ◽  
Vol 18 (11) ◽  
pp. 4637-4647 ◽  
Author(s):  
Florence Jollivet ◽  
Graça Raposo ◽  
Ariane Dimitrov ◽  
Rachid Sougrat ◽  
Bruno Goud ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Complex ◽  
De Novo ◽  
Living Cells ◽  
Integrative Model ◽  
Interphase Cells ◽  
Golgi Structure ◽  
Dynamics And Function ◽  
And Function ◽  
Drug Free

The Golgi complex is characterized by its unique morphology of closely apposed flattened cisternae that persists despite the large quantity of lipids and proteins that transit bidirectionally. Whether such a structure is maintained through endoplasmic reticulum (ER)-based recycling and auto-organization or whether it depends on a permanent Golgi structure is strongly debated. To further study Golgi maintenance in interphase cells, we developed a method allowing for a drug-free inactivation of Golgi dynamics and function in living cells. After Golgi inactivation, a new Golgi-like structure, containing only certain Golgi markers and newly synthesized cargos, was produced. However, this structure did not acquire a normal Golgi architecture and was unable to ensure a normal trafficking activity. This suggests an integrative model for Golgi maintenance in interphase where the ER is able to autonomously produce Golgi-like structures that need pre-existing Golgi complexes to be organized as morphologically normal and active Golgi elements.

scholarly journals Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wondwossen M Yeshaw ◽  
Marianne van der Zwaag ◽  
Francesco Pinto ◽  
Liza L Lahaye ◽  
Anita IE Faber ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Mammalian Cells ◽  
Lipid Droplets ◽  
Neurodegenerative Disorder ◽  
Close Contact ◽  
Mitochondrial Morphology ◽  
Published Data ◽  
Membrane Contact Sites ◽  
Contact Sites

The VPS13A gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It is unknown what the consequences are of impaired function of VPS13A at the subcellular level. We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. VPS13A is localized at sites where the endoplasmic reticulum and mitochondria are in close contact. VPS13A interacts with the ER residing protein VAP-A via its FFAT domain. Interaction with mitochondria is mediated via its C-terminal domain. In VPS13A-depleted cells, ER-mitochondria contact sites are decreased, mitochondria are fragmented and mitophagy is decreased. VPS13A also localizes to lipid droplets and affects lipid droplet motility. In VPS13A-depleted mammalian cells lipid droplet numbers are increased. Our data, together with recently published data from others, indicate that VPS13A is required for establishing membrane contact sites between various organelles to enable lipid transfer required for mitochondria and lipid droplet related processes.

scholarly journals Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperone DNAJC3

2021 ◽  
Vol 9 ◽  
Author(s):  
Matthew J. Jennings ◽  
Denisa Hathazi ◽  
Chi D. L. Nguyen ◽  
Benjamin Munro ◽  
Ute Münchberg ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cholesterol Homeostasis ◽  
Mitochondrial Morphology ◽  
Unfolded Protein ◽  
Recessive Mutations ◽  
Proteomic Approach ◽  
Intracellular Lipid Accumulation ◽  
Increased Sensitivity ◽  
The Unfolded Protein Response ◽  
And Function

Recessive mutations in DNAJC3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms, we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with DNAJC3 mutations detected cellular accumulation of lipids and an increased sensitivity to cholesterol stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, and a defect of amyloid precursor protein. In line with the results of previous studies, we describe here alterations in mitochondrial morphology and function, as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects lipid/cholesterol homeostasis, leading to UPR activation, β-amyloid accumulation, and impairment of mitochondrial oxidative phosphorylation.

scholarly journals The Endoplasmic Reticulum-Mitochondria Encounter Structure and its Regulatory Proteins

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110644
Author(s):  
Javairia Y. Cheema ◽  
Jiajia He ◽  
Wenfan Wei ◽  
Chuanhai Fu
Keyword(s):  
Endoplasmic Reticulum ◽  
Regulatory Proteins ◽  
Contact Sites ◽  
Constitutive Components ◽  
And Function

In fungi, the endoplasmic reticulum-mitochondria encounter structure (ERMES) is present between the endoplasmic reticulon (ER) and mitochondria to promote the formation of the ER-mitochondria contact sites. Four constitutive components (Mmm1, Mdm12, Mdm34, and Mdm10) assemble to form the ERMES complex while regulator proteins are required for regulating the organization and function of the ERMES complex. Multiple regulator proteins, including Gem1, Lam6, Tom7, and Emr1, of the ERMES complex, have been identified recently. In this review, we discuss the organization of the ERMES complex and the roles of the regulator proteins of the ERMES complex.

scholarly journals SAC1 Degrades its Lipid Substrate PtdIns4P in the Endoplasmic Reticulum to Maintain a Steep Chemical Gradient with Donor Membranes

2018 ◽  
Author(s):  
James P. Zewe ◽  
Rachel C. Wills ◽  
Sahana Sangappa ◽  
Brady D. Goulden ◽  
Gerald R. V. Hammond
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Homeostasis ◽  
Chemical Gradient ◽  
Vesicular Traffic ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Catalytic Domains ◽  
In Trans ◽  
Membrane Contact ◽  
And Function

AbstractGradients of PtdIns4P between organelle membranes and the endoplasmic reticulum (ER) are thought to drive counter-transport of other lipids via non-vesicular traffic. This novel pathway requires the SAC1 phosphatase to degrade PtdIns4P in a “cis” configuration at the ER to maintain the gradient. However, SAC1 has also been proposed to act in “trans” at membrane contact sites, which could oppose lipid traffic. It is therefore crucial to determine which mode SAC1 uses in living cells. We report that acute inhibition of SAC1 causes accumulation of PtdIns4P in the ER, that SAC1 does not enrich at membrane contact sites, and that SAC1 has little activity in “trans”, unless a linker is added between its ER-anchored and catalytic domains. The data reveal an obligate “cis” activity of SAC1, supporting its role in non-vesicular lipid traffic and implicating lipid traffic more broadly in inositol lipid homeostasis and function.

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