Emerging Roles of the MICOS Complex in Cristae Dynamics and Biogenesis

Anand, Ruchika; Reichert, Andreas S.; Kondadi, Arun Kumar

doi:10.3390/biology10070600

Cited by 51 publications

(41 citation statements)

References 105 publications

(189 reference statements)

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“…This proves the importance of CJ in maintaining the heterogeneity of ΔѰm between different regions of the IM, possibly by acting as a diffusion barrier for protons or other metabolites (Anand et al, 2021). It was also observed that cristae vesicles generated due to the detachment of CJ from the IBM in MIC10 or OPA1 KO cells had hyperpolarized mitochondria (Anand et al, 2021;Wolf et al, 2019). This could perhaps be extrapolated to MIC60 KD or KO cells although, experiments are needed to measure the changes in ΔѰm in cells subjected to MIC60 KD or KO.…”

Section: Mic60 Depletion Can Affect Mitochondrial Ros Levelsmentioning

confidence: 62%

“…Studies reported previously that depletion in MICOS sub-units like MIC13, MIC10 or MIC60 could Discussion decrease the heterogeneity in the ΔѰm between CM and IBM. This proves the importance of CJ in maintaining the heterogeneity of ΔѰm between different regions of the IM, possibly by acting as a diffusion barrier for protons or other metabolites (Anand et al, 2021). It was also observed that cristae vesicles generated due to the detachment of CJ from the IBM in MIC10 or OPA1 KO cells had hyperpolarized mitochondria (Anand et al, 2021;Wolf et al, 2019).…”

Section: Mic60 Depletion Can Affect Mitochondrial Ros Levelsmentioning

confidence: 65%

“…CM have a higher ΔѰm as compared to IBM. It is also reported that CM within that same mitochondria can also have heterogeneity in ΔѰm (Anand et al, 2021). It was also shown that MIC60 or MIC10 KO could decrease ΔѰm between the IBM and CM.…”

Section: Mic60 Depletion Can Affect Mitochondrial Ros Levelsmentioning

confidence: 86%

“…For example, drawing the TOM and TIM complexes within close proximity with each other, that enhances the spatial and temporal fidelity of protein translocation across both membranes (Donzeau et al, 2000;Schülke et al, 1997). These membrane contact sites exist only temporarily and are highly dynamic (Anand et al, 2021). Additionally, there are highly stable contact sites that are unaltered even under harsh physical conditions such as changes in osmolarity, whereas the rest of the IM disintegrates and separates from the OM (Reichert & Neupert, 2002;Hackenbrock, 1966).…”

Section: Mitochondrial Proteins Involved In Intra-mitochondrial Conta...mentioning

confidence: 99%

“…Due to the drastic effects of deletion of one or more MICOS components on the overall mitochondrial ultra-structure (Figure 1.7), it is a very important determinant for proper regulation and functioning of mitochondrial processes such as cellular signalling, metabolism, and energetics Kondadi et alet al, 2020;. This is further essential for proper and efficient respiration, apoptosis, and maintenance of mitochondrial quality control (Anand et al, 2021). Several pathophysiological conditions have been discovered in direct or indirect relation to MICOS sub-units (Colina-Tenorio et al, 2020;Eramo et al, 2020;Mukherjee et al, 2021).…”

Section: 4mentioning

confidence: 99%

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Decoding and influencing mitochondrial inner membrane ultra-structure biogenesis

Mukherjee¹

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Section: Mic60 Depletion Can Affect Mitochondrial Ros Levelsmentioning

confidence: 62%

Section: Mic60 Depletion Can Affect Mitochondrial Ros Levelsmentioning

confidence: 65%

Section: Mic60 Depletion Can Affect Mitochondrial Ros Levelsmentioning

confidence: 86%

Section: Mitochondrial Proteins Involved In Intra-mitochondrial Conta...mentioning

confidence: 99%

Section: 4mentioning

confidence: 99%

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Decoding and influencing mitochondrial inner membrane ultra-structure biogenesis

Mukherjee¹

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Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue

Crabtree,

Neikirk,

Marshall

et al. 2023

Advanced Biology

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Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content and abundance. The physiological function and bioenergetic capacity of mitochondria are connected to the structure, folding, and organization of its inner‐membrane cristae. During the aging process, mitochondrial dysfunction is observed, and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells. Therefore, it is hypothesized that significant morphological changes in BAT mitochondria and cristae will be present with aging. A quantitative 3D electron microscopy approach is developed to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, the 3D morphology of mitochondrial cristae is investigated in adult (3‐month) and aged (2‐year) murine BAT tissue via serial block face‐scanning electron microscopy (SBF‐SEM) and 3D reconstruction software for manual segmentation, analysis, and quantification. Upon investigation, an increase is found in mitochondrial volume, surface area, and complexity and decreased sphericity in aged BAT, alongside significant decreases in cristae volume, area, perimeter, and score. Overall, these data define the nature of the mitochondrial structure in murine BAT across aging.

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Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes

Shao,

Killion,

Oliver

et al. 2024

Journal Cellular Physiology

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The sorting and assembly machinery (SAM) Complex is responsible for assembling β‐barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block‐face‐scanning electron microscopy and computer‐assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50‐deficient myotubes from mice and humans with wild‐type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography‐Mass Spectrometry‐based metabolomics to explore differential changes in WT and Sam50‐deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50‐deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß‐Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50‐deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50‐deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle.

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Emerging Roles of the MICOS Complex in Cristae Dynamics and Biogenesis

Cited by 51 publications

References 105 publications

Decoding and influencing mitochondrial inner membrane ultra-structure biogenesis

Decoding and influencing mitochondrial inner membrane ultra-structure biogenesis

Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue

Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes

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