Orphan proteins of unknown function in the mitochondrial intermembrane space proteome: New pathways and metabolic cross-talk.

The mitochondrial intermembrane space (IMS) is involved in protein transport, lipid homeostasis and metal ion exchange, while further acting in signalling pathways such as apoptosis. Regulation of these processes involves protein modifications, as well as stress-induced import or release of proteins and other signalling molecules. Even though the IMS is the smallest sub-compartment of mitochondria, its redox state seems to be tightly regulated. However, the way in which this compartment participates in the cross-talk between the multiple organelles and the cytosol is far from understood. Here we focus on newly identified IMS proteins that may represent future challenges in mitochondrial research. We present an overview of the import pathways, the recently discovered new components of the IMS proteome and how these relate to key aspects of cell signalling and progress made in stem cell and cancer research.

Oxidative folding in the mitochondrial intermembrane space: A regulated process important for cell physiology and disease.

Mitochondria are fundamental organelles with a complex internal architecture that fulfill important diverse functions including iron-sulfur cluster assembly and cell respiration. Intense work for more than 30 years has identified the key protein import components and the pathways involved in protein targeting and assembly. More recently, oxidative folding has been discovered as one important mechanism for mitochondrial proteostasis whilst several human disorders have been linked to this pathway. We describe the molecular components of this pathway in view of their putative redox regulation and we summarize available evidence on the connections of these pathways to human disorders.

Oxidative protein biogenesis and redox regulation in the mitochondrial intermembrane space.

Mitochondria are organelles that play a central role in cellular metabolism, as they are responsible for processes such as iron/sulfur cluster biogenesis, respiration and apoptosis. Here, we describe briefly the various protein import pathways for sorting of mitochondrial proteins into the different subcompartments, with an emphasis on the targeting to the intermembrane space. The discovery of a dedicated redox-controlled pathway in the intermembrane space that links protein import to oxidative protein folding raises important questions on the redox regulation of this process. We discuss the salient features of redox regulation in the intermembrane space and how such mechanisms may be linked to the more general redox homeostasis balance that is crucial not only for normal cell physiology but also for cellular dysfunction.

Development of an Oriented Co-Culture System Using 3D Scaffolds Fabricated via Non-Linear Lithography.

Damage in the Peripheral Nervous System (PNS) is related to numerous neurodegenerative diseases and has consequently drawn the attention of Tissue Engineering (TE), which is considered a promising alternative to already established methods such as surgery and autografts. TE focuses on the design, optimization, and use of scaffolds in vitro and in vivo. In this work, the authors used a novel scaffold geometry fabricated via Multiphoton Lithography (MPL), a commonly used fabrication method, for the mono- and co-cultures of glial Schwann (SW10) and neuronal Neuro-2a (N2a) cells. Both cell types have already been used for the study of various neurodegenerative diseases. However, their focus has been on only one of the cell types at a time, with studies regarding their co-culture only recently documented. Here, the suitability of the fabricated scaffolds has been explored and the effects of topography on SW10 and N2a behavior have been investigated. Our findings demonstrate that scaffold co-culture systems favor the presence of neurites compared to mono-cultures at 21 days (31.4 ± 5.5% and 15.4 ± 5.4%, respectively), while there is also a significant decrease in long neurites in the mono-culture over time (45.3 ± 15.9% at 7 days versus 15.4 ± 5.4% at 21 days). It has been shown that the scaffolds can successfully manipulate cell growth, elongation, and morphology, and these results can form a basis for the development of an experimental model for the study of PNS-related diseases and understanding of key cell functions such as myelination.

Fabrication of Biomimetic 2D Nanostructures through Irradiation of Stainless Steel Surfaces with Double Femtosecond Pulses.

Femtosecond laser induced changes on the topography of stainless steel with double pulses is investigated to reveal the role of parameters such as the fluence, the energy dose and the interpulse delay on the features of the produced patterns. Our results indicate that short pulse separation (Δτ = 5 ps) favors the formation of 2D Low Spatially Frequency Laser Induced Periodic Surface Structures (LSFL) while longer interpulse delays (Δτ = 20 ps) lead to 2D High Spatially Frequency LIPSS (HSFL). The detailed investigation is complemented with an analysis of the produced surface patterns and characterization of their wetting and cell-adhesion properties. A correlation between the surface roughness and the contact angle is presented which confirms that topographies of variable roughness and complexity exhibit different wetting properties. Furthermore, our analysis indicates that patterns with different spatial characteristics demonstrate variable cell adhesion response which suggests that the methodology can be used as a strategy towards the fabrication of tailored surfaces for the development of functional implants.

The role of mechanobiology on the Schwann cell response: A tissue engineering perspective.

Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS), do not only form myelin sheaths thereby insulating the electrical signal propagated by the axons, but also play an essential role in the regeneration of injured axons. SCs are inextricably connected with their extracellular environment and the mechanical stimuli that are received determine their response during development, myelination and injuries. To this end, the mechanobiological response of SCs is being actively researched, as it can determine the suitability of fabricated scaffolds for tissue engineering and regenerative medicine applications. There is growing evidence that SCs are sensitive to changes in the mechanical properties of the surrounding environment (such as the type of material, its elasticity and stiffness), different topographical features provided by the environment, as well as shear stress. In this review, we explore how different mechanical stimuli affect SC behaviour and highlight the importance of exploring many different avenues when designing scaffolds for the repair of PNS injuries.