*6.3.4. Cytosol*

Several signals coming from the cytosol can induce MMP. These include: metabolites such as glucose 6-phospate and palmitate, ROS and activation of certain kinases: GSK3β, protein kinase C (PKC) δ, [65] and members of the JNK signalling pathway [38,66]. On the other hand, other molecules inactivate PTP and protect mitochondrial membrane from permeabilization, inhibiting apoptosis. These include: metabolites (ATP, glucose, NADH, UTP, etc.), antiapoptotic Bcl-2 family members, antioxidant enzymes such as glutathiones S transferase and prosurvival kinases such as Akt. In this sense, Akt can inhibit apoptosis by several mechanisms: activation of NFkB [67], inactivation of GSK3β and caspases and through hexokinase II-dependent mechanisms [12].

## *6.3.5. Cytoskeleton*

The cytoskeleton is composed of microtubules, microfilaments and intermediate filaments that play important roles in cell motility, polarity, attachment, shape maintenance, etc. Adherent cells can undergo a specific type of caspase-dependent cell death called **anoikis**

when they become detached from the extracellular matrix or neighbouring cells [68,69]. Besides its well-established role in mitosis, cytoskeleton components can modulate mitochondria. For example, microtubules sequester BH3-only proteins Bim and Bmf, which interact with dynein [70]. Gelsolin has anti-apoptotic effect by closing the VDAC channel [71]. Actin can also modulate VDAC closure [69,72].
